If the DNA Sequence Remains Unchanged, Why Does Gene Expression Change? Core Mechanisms and Research Methods of Epigenetic Regulation
If the DNA Sequence Remains Unchanged, Why Does Gene Expression Change? Core Mechanisms and Research Methods of Epigenetic Regulation
1. Why Can the Same Set of DNA Give Rise to Different Cell Fates?
Most somatic cells in the human body contain essentially the same deoxyribonucleic acid (DNA) sequence, yet different cells differ in morphology, function, and gene expression patterns. Hepatocytes express metabolism-related genes; neurons express genes involved in synaptic transmission; macrophages express genes associated with immune recognition and inflammatory responses; and T cells have the capacity for antigen recognition, proliferation, and effector differentiation.
These differences arise because different cells “read” the same genome in different ways. Cell fate depends on which genes are activated, which genes are repressed, and which genes can respond rapidly upon stimulation. During cell differentiation, the epigenome is reorganized, allowing the same DNA to form different regulatory states in different cells. This is an important basis for the distinct functions of different cell types. This process can be summarized as follows:
Same DNA sequence → Different combinations of transcription factors → Different chromatin accessibility states → Different patterns of DNA methylation and histone modifications → Different gene expression programs → Different cell fates and functions
It should be noted that this process is not a strictly one-way chain. Transcription factors, chromatin state, DNA methylation, and histone modifications interact with one another and form feedback regulatory relationships.
Cell fate is jointly determined by DNA sequence, transcription factors, chromatin state, and epigenetic modifications. DNA provides genetic information; transcription factors determine which regulatory regions are recognized; and chromatin state and epigenetic modifications influence whether these regions can be effectively accessed and interpreted.
2. What Is Epigenetics? Changing Expression States Without Altering the DNA Sequence
In a broad sense, epigenetic regulation refers to the process by which gene expression states are altered through DNA modifications, histone modifications, chromatin structure, and related regulatory factors without changing the DNA base sequence. In the strict sense, epigenetics also emphasizes that these expression states can be maintained to some extent during cell division. Its core questions are: “Is a gene readily expressed?” “In which cell types is it expressed?” and “Can it be activated upon stimulation?” Epigenetic regulation has three basic characteristics.
2.1 Regulability
Epigenetic states can change with developmental stage, cell differentiation, inflammatory stimulation, metabolic status, drug treatment, and disease progression. Many chromatin modifications and accessibility states are not fixed; rather, they are dynamically adjusted according to the state of the cell.
2.2 A Certain Degree of Stability
Some epigenetic states can be maintained after cell division, allowing cells to preserve their original identity. For example, differentiated cells usually continue to express genes required for their own cell type while repressing genes associated with other lineages. This stability is an important basis for maintaining the function of tissue cells.
2.3 Reversibility
Modifications such as DNA methylation, histone acetylation, and histone methylation can be written, removed, or recognized by corresponding enzyme systems. Therefore, epigenetic regulation can both maintain cellular states and be reshaped by external stimuli or pharmacological intervention. Modern research has advanced epigenetics from a descriptive phenomenon to a molecular mechanism that can be detected and intervened in.
3. Three Core Mechanisms: DNA Methylation, Histone Modifications, and Chromatin Accessibility
Epigenetic regulation involves multiple mechanisms, including DNA methylation, histone modifications, chromatin accessibility, chromatin remodeling, non-coding ribonucleic acid (RNA), and three-dimensional genome organization. This article focuses on three categories most closely linked to signaling pathways, disease mechanisms, and commonly used experimental methods: DNA methylation, histone modifications, and chromatin accessibility.
3.1 DNA Methylation: Influencing Long-Term Gene Expression States
DNA methylation usually refers to methylation at the carbon-5 position of cytosine, forming 5-methylcytosine (5mC). In mammals, DNA methylation occurs mainly at cytosine-phosphate-guanine (CpG) dinucleotide sites. In certain cell types, such as embryonic stem cells and neurons, non-CpG methylation also has biological significance.
Hypermethylation of promoter regions, especially CpG island promoters, is usually associated with transcriptional repression. The function of DNA methylation depends on its genomic location: its significance is not the same in promoters, enhancers, gene bodies, and repetitive sequences.
The writing reaction of DNA methylation can be simplified as follows:
Cytosine + S-adenosylmethionine (SAM)
↓ DNA methyltransferase (DNMT)
5-methylcytosine (5mC) + S-adenosylhomocysteine (SAH)
Among these enzymes, DNA methyltransferases (DNMTs) are responsible for writing methylation modifications. The ten-eleven translocation (TET) protein family can oxidize 5-methylcytosine (5mC) into products such as 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC), and 5-carboxylcytosine (5caC), and participates in DNA demethylation through passive dilution or DNA repair-related processes.
DNA methylation plays important roles in cell differentiation, genome stability, genomic imprinting, X-chromosome inactivation, repression of repetitive sequences, and tumorigenesis.
3.2 Histone Modifications: Regulating Chromatin Activity and Protein Recruitment
In eukaryotic cells, DNA wraps around histone octamers to form nucleosomes. Histone tails can undergo various post-translational modifications, including acetylation, methylation, phosphorylation, ubiquitination, and lactylation. These modifications influence chromatin structure, transcription factor binding, and the recruitment of regulatory proteins.
Histone acetylation is usually associated with chromatin opening and transcriptional activation. One reason is that lysine acetylation neutralizes positive charges, weakens the interaction between histones and DNA, and provides binding sites for reader proteins containing bromodomains.
The histone acetylation reaction can be simplified as follows:
Histone-Lys-NH₃⁺ + acetyl-CoA
↓ Lysine acetyltransferase (KAT/HAT)
Histone-Lys-NHCOCH₃ + CoA-SH + H⁺
Lysine acetyltransferases (KATs; also commonly referred to as histone acetyltransferases, HATs) are responsible for writing acetylation modifications; histone deacetylases (HDACs) are responsible for removing acetylation modifications.
The function of histone methylation depends more strongly on the modification site. For example, H3K4me3 is usually enriched at active promoters; H3K27ac is commonly found at active promoters and enhancers; H3K27me3 is usually associated with Polycomb-mediated gene repression; and H3K9me3 is often associated with heterochromatin and silencing of repetitive sequences.
Common Histone Mark | Common Location or State | Common Functional Meaning |
H3K4me3 | Active promoters | Associated with transcription initiation |
H3K27ac | Active enhancers and promoters | Associated with activation of regulatory elements |
H3K4me1 | Candidate enhancers or primed/poised enhancer regions | Commonly used to indicate enhancer potential |
H3K27me3 | Polycomb-repressed regions | Associated with repression of developmental genes |
H3K9me3 | Heterochromatin and repetitive sequences | Associated with stable silencing and genome stability |
Histone modifications do not act alone. Instead, they work together with transcription factors, DNA methylation, chromatin accessibility, and chromatin remodeling complexes to influence gene expression.
3.3 Chromatin Accessibility: Influencing Whether Regulatory Elements Can Be Read
Chromatin accessibility describes whether a particular DNA region can be readily contacted by transcription factors, RNA polymerase, and regulatory proteins. Open chromatin usually means that regulatory regions are easier to recognize, whereas compact chromatin restricts protein binding. Chromatin accessibility reflects the usable state of regulatory regions and is an important indicator for understanding gene expression regulation.
Chromatin State | Structural Features | Regulatory Outcome |
Open chromatin | Nucleosomes are arranged more loosely, and regulatory regions are easier for proteins to access | Transcription factors bind more easily, and genes are more readily activated |
Compact chromatin | Nucleosomes are arranged more tightly, and regulatory regions are less accessible | Transcription factor binding is restricted, and gene expression is suppressed |
Chromatin accessibility is critical for signal responses. When exposed to the same inflammatory factors, growth factors, or metabolic stimuli, different cells can respond in completely different ways. One reason is whether the enhancer or promoter of the target gene is already in an accessible state. If a regulatory region is open, transcription factors can bind rapidly after entering the nucleus; if the regulatory region is closed, the target gene may not be fully expressed even when the upstream signal is activated.
4. Writers, Erasers, and Readers: The Executors of Epigenetic Regulation
Epigenetic regulation is carried out by a group of proteins with enzymatic activity or recognition functions. A commonly used framework is Writers, Erasers, and Readers—that is, proteins that write, erase, and read epigenetic marks.
4.1 Writers: Writing Modifications
Writers are responsible for adding chemical modifications to DNA or histones.
DNMT1, DNMT3A, and DNMT3B write DNA methylation. KATs/HATs, such as p300 and CBP, write histone acetylation. EZH2 is the catalytic subunit of polycomb repressive complex 2 (PRC2) and participates in writing H3K27me3. The KMT family is responsible for histone lysine methylation at different sites.
4.2 Erasers: Removing Modifications
Erasers are responsible for removing modifications, giving epigenetic states reversibility.
The HDAC and SIRT families can remove histone acetylation. The KDM family can remove histone methylation. The TET family participates in DNA demethylation-related processes by oxidizing 5mC.
4.3 Readers: Recognizing Modifications and Recruiting Functional Complexes
Readers recognize specific modifications and recruit protein complexes involved in transcriptional activation, transcriptional repression, or chromatin remodeling.
BET family proteins recognize acetylated lysine through bromodomains and participate in enhancer activation and transcription elongation. MeCP2 and MBD family proteins can recognize methylated DNA and associate with transcriptional repression complexes. Domains such as PHD, chromodomain, and Tudor domains can recognize different methylated histone marks.
Modification Type | Writers | Erasers | Readers | Common Functions |
DNA methylation | DNMT1, DNMT3A, DNMT3B | TET1, TET2, TET3 | MeCP2, MBD family | Gene silencing, maintenance of cell identity, genome stability |
Histone acetylation | p300, CBP, other KATs/HATs | HDACs, SIRT family | BET family, other bromodomain proteins | Chromatin opening, enhancer activation, transcriptional promotion |
Histone methylation | EZH2, SETD2, other KMTs | LSD1, KDM family | PHD, chromodomain, Tudor, etc. | Site-dependent regulation; can promote or repress transcription |
The core logic of epigenetic regulation: from chromatin state to gene expression output.
The same DNA sequence can give rise to different gene expression programs because of different epigenetic states. DNA methylation, histone modifications, and chromatin accessibility jointly influence the access of transcription factors and RNA polymerase II to regulatory elements. Writers, Erasers, and Readers participate in the writing, removal or conversion, and recognition of epigenetic modifications. Signaling pathways respond to external stimuli through transcription factors, while chromatin state determines whether target genes are readily regulated.
5. How Epigenetics Affects Disease: Cancer, Inflammation, Immune Memory, and Cell Differentiation
Epigenetic abnormalities do not change the coding sequence of DNA, but they do change how cells use the genome. Therefore, they can influence tumorigenesis, inflammatory responses, immune memory, cell differentiation, and therapeutic tolerance.
5.1 Cancer: Aberrant Expression Programs Drive Malignant Phenotypes
Tumor cells often exhibit abnormal DNA methylation, abnormal histone modifications, altered chromatin accessibility, and enhancer remodeling. Aberrant hypermethylation of tumor suppressor gene promoters can reduce their expression; activation of oncogene-associated enhancers can enhance the expression of genes that promote proliferation or resist apoptosis; and abnormal activity of epigenetic regulators such as DNMTs, HDACs, EZH2, and BET proteins can contribute to tumor progression and therapeutic tolerance. The core of cancer epigenetics research is to understand how tumor cells reshape gene expression programs beyond changes in gene sequence.
5.2 Inflammation: Determining Whether Inflammatory Genes Can Be Rapidly Opened
Inflammatory responses depend on transcription factors such as NF-κB, AP-1, STAT, and IRF. However, whether these transcription factors can effectively activate target genes depends on whether the target sites are in an open chromatin state, whether they carry active regulatory marks such as H3K27ac, and whether they can recruit transcription-related factors such as p300/CBP and RNA polymerase II. Inflammatory signaling pathways transmit external stimuli into the nucleus, while epigenetic states determine whether these signals can be converted into effective gene expression output.
5.3 Immune Memory: Allowing Cells to Retain the Effects of Past Stimulation
After immune cells experience infection, vaccination, chronic inflammation, or stimulation from the tissue microenvironment, they may form relatively stable changes in chromatin state. Processes such as T cell memory, T cell exhaustion, and trained immunity in macrophages are all associated with changes in enhancer activity, DNA methylation, and histone modifications. Research on trained immunity has shown that innate immune cells and hematopoietic progenitor cells can undergo epigenetic and metabolic reprogramming, leading to altered responses upon restimulation. This indicates that immune memory does not exist only at the level of antigen receptors; it can also be reflected in long-term changes in gene regulatory states.
5.4 Cell Differentiation: Stabilizing Cell Identity and Restricting Aberrant Expression
Cell differentiation requires two processes to occur simultaneously: genes required for the given cell type must be activated, while genes associated with other cell types must be silenced. Through changes in DNA methylation, histone modifications, and chromatin accessibility, epigenetic mechanisms help cells stabilize their own identity.
For example, when hematopoietic stem cells differentiate toward myeloid or lymphoid lineages, this process is accompanied by enhancer selection, opening of transcription factor binding sites, DNA methylation remodeling, and changes in histone modifications. Transcription factors provide the direction of differentiation, while epigenetic states help establish and maintain that direction.
6. The Relationship Between Epigenetics and Signaling Pathways: Transcription Factors Respond, Chromatin Determines Accessibility
Signaling pathways and epigenetic regulation are not independent systems. Signaling pathways usually transmit external stimuli into the nucleus through transcription factors, while epigenetic states determine whether transcription factors can access target DNA, recruit co-activators, and form stable gene expression output.
Taking inflammatory signaling as an example:
LPS, TNF-α, IL-6, and other stimuli
↓
Activation of transcription factors such as NF-κB, AP-1, and STAT
↓
Transcription factors enter the nucleus
↓
Whether the regulatory regions of target genes are open determines whether transcription factors can bind sufficiently
↓
Co-activators such as p300/CBP are recruited, and H3K27ac increases
↓
Inflammatory gene expression is enhanced
This relationship can be summarized as follows:
Question | What Signaling Pathways Mainly Answer | What Epigenetics Mainly Answers |
Has the cell received a stimulus? | Whether receptors and kinases are activated | Does not directly answer this |
Which transcription factors are activated? | Whether NF-κB, STAT, AP-1, IRF, etc. enter the nucleus | Does not directly answer this |
Can transcription factors bind target sites? | Provides nuclear transcription factors | Determined by chromatin openness and nucleosome distribution |
Can genes be stably expressed? | Provides the initiating signal | Jointly influenced by enhancer activity, histone modifications, and DNA methylation |
Does the cell retain a long-term state? | Usually relatively transient | Can form relatively stable regulatory states |
Therefore, when studying a signaling pathway, detecting protein phosphorylation alone usually only indicates whether the signal has been activated. To explain why some genes are expressed while others are not, it is also necessary to analyze chromatin accessibility, histone modifications, and DNA methylation.
7. Common Experimental Methods: ChIP, CUT&Tag, ATAC-seq, Methylation Sequencing, and RNA-seq
Experimental design in epigenetic research should focus on three questions: whether regulatory regions are open, whether they carry specific modifications or bind specific proteins, and whether gene expression ultimately changes.
7.1 ChIP: Detecting the Genomic Distribution of Proteins or Histone Modifications
Chromatin immunoprecipitation (ChIP) uses antibodies to enrich DNA fragments associated with specific proteins or histone modifications. When combined with quantitative polymerase chain reaction (qPCR), it can detect specific loci; when combined with high-throughput sequencing, it becomes ChIP-seq, which is used to map transcription factor binding sites or histone modification distributions across the genome.
ChIP-seq can be used to detect DNA-binding proteins and histone chemical modifications and is an important technique in epigenomic research. Common targets include H3K27ac, H3K4me3, H3K27me3, H3K9me3, RNA polymerase II, as well as transcription factors or structural proteins such as NF-κB p65, STAT3, and CTCF.
7.2 CUT&Tag: A Low-Input Epigenomic Profiling Technique
Cleavage under targets and tagmentation (CUT&Tag) uses antibodies to recognize target proteins or histone modifications, and then uses protein A/G-fused Tn5 transposase to insert sequencing adapters near the target.
CUT&Tag can be used to map histone modifications, RNA polymerase II, and transcription factors, and is suitable for low-cell-number and single-cell sample studies. Compared with traditional ChIP, CUT&Tag usually has lower background and requires fewer starting cells. However, experimental results still depend on antibody quality, nuclei preparation, and library quality control.
7.3 ATAC-seq: Detecting Chromatin Accessibility
Assay for transposase-accessible chromatin with sequencing (ATAC-seq) uses Tn5 transposase to preferentially enter open chromatin regions and insert sequencing adapters, thereby identifying open chromatin sites genome-wide. ATAC-seq can be used to analyze promoters, enhancers, potential transcription factor binding regions, and differences in cellular states.
Motif enrichment or footprinting analysis based on ATAC-seq can only suggest potential transcription factor activity or binding possibility; it cannot replace TF ChIP-seq, CUT&Tag, or CUT&RUN for validating actual binding. ATAC-seq is often used together with ChIP-seq, CUT&Tag, and RNA-seq to determine whether open regions have features of active enhancers and whether they are associated with changes in gene expression.
7.4 Methylation Sequencing: Detecting DNA Methylation States
DNA methylation can be detected using bisulfite sequencing, targeted methylation sequencing, pyrosequencing, whole-genome bisulfite sequencing (WGBS), and other methods. Bisulfite treatment converts unmethylated cytosine into uracil, while methylated cytosine is relatively retained, allowing the methylation status of CpG sites to be inferred after sequencing.
If the study focuses on methylation of a specific gene promoter, targeted methylation sequencing or pyrosequencing can be used. If a genome-wide methylation map is required, WGBS or other methylome technologies can be selected.
7.5 RNA-seq: Detecting the Expression Output of Epigenetic Regulation
RNA sequencing (RNA-seq) itself is not an epigenetic detection technique, but it is an important method for determining whether epigenetic changes produce functional output. Without expression data, it is often difficult to determine the biological significance of epigenetic maps.
A relatively complete research design usually includes:
ATAC-seq: Which regions are open?
ChIP-seq / CUT&Tag: What modifications do these regions carry, or what proteins bind to them?
Methylation sequencing: Do key regions show changes in DNA methylation?
RNA-seq: Does the expression of related genes change?
Functional experiments: Does the cellular phenotype change accordingly?
Epigenomic readouts are mostly correlative evidence. To prove causality, they need to be combined with functional validation approaches such as inhibitors, gene knockdown/knockout, rescue with mutants, CRISPR-based epigenome editing, or reporter assays.
7.6 Common Technology Selection Table
Research Question | Recommended Methods | Main Readouts | Suitable Questions to Answer |
Whether a transcription factor binds a target region | ChIP-qPCR, ChIP-seq, CUT&Tag | Enrichment at the target region, binding peaks | Whether NF-κB, STAT, CTCF, etc. bind a specific regulatory region |
Whether a histone modification changes | ChIP-qPCR, ChIP-seq, CUT&Tag | Signals such as H3K27ac, H3K4me3, H3K27me3 | Whether enhancer, promoter, or repressive chromatin states change |
Whether chromatin is open | ATAC-seq | Open chromatin peaks, transcription factor motif enrichment | Whether regulatory regions of target genes are more accessible to transcription factors |
Whether DNA methylation changes | Methylation sequencing, WGBS | CpG methylation percentage | Whether methylation changes occur at promoters, enhancers, or gene bodies |
Whether expression output changes | RNA-seq, qPCR | Gene expression levels | Whether epigenetic changes are converted into expression differences |
Whether regulation is causal | Inhibitors, gene knockdown, knockout, CRISPR epigenome editing | Changes in epigenetic marks, expression, and phenotype | Whether a specific epigenetic factor drives the target phenotype |
8. Summary: Epigenetics Is a Long-Term Regulatory Layer of Gene Expression
The core question answered by epigenetic regulation is: if the DNA sequence has not changed, why does the gene expression state change?
The answer can be summarized in four points.
① The same set of DNA forms different chromatin states in different cells, allowing different cells to selectively express different genes.
② DNA methylation, histone modifications, and chromatin accessibility jointly influence whether genes are active, repressed, or poised for activation.
③ Writers, Erasers, and Readers provide mechanisms for writing, removing, and recognizing epigenetic modifications; therefore, epigenetic regulation has both stability and reversibility.
④ Signaling pathways transmit external stimuli through transcription factors, while epigenetic states determine
Epigenetics is a regulatory layer of gene expression that spans regulatory regions across the genome. It determines how cells use the same set of genetic information and also explains many long-term and stable expression changes involved in cell fate, tumor progression, inflammatory responses, and immune memory.
9. Classification Table of Representative Chemicals Related to Epigenetic Regulation
Table 1. Basic Reagents for Epigenetic Experimental Methods and Sample Processing
Category | CAS No. | Aladdin Cat. No. | Name | Specification or Purity | Product Features and Applications |
DNA alkaline denaturation reagent | 1310-73-2 | S111498 | Sodium hydroxide | Superior-grade reagent, ≥96% | Used for DNA denaturation, pretreatment before bisulfite conversion, and sample preparation for methylation detection |
Bisulfite conversion reagent | 7631-90-5 | Sodium bisulfite | Superior-grade reagent | Used for bisulfite conversion in DNA methylation detection; suitable for CpG-site methylation analysis | |
Chromatin crosslinking reagent | 50-00-0 | Formaldehyde solution | Molecular biology grade, ≥36.0% in H₂O (T), contains 10–15% methanol as stabilizer | Used for chromatin immunoprecipitation, protein-DNA crosslinking, and studies of transcription factor binding sites | |
Crosslinking quenching reagent | 56-40-6 | Glycine | UltraBio™, molecular biology grade, ultrapure grade, ≥99% (NT) | Used to terminate formaldehyde crosslinking reactions; suitable for sample processing in chromatin immunoprecipitation and related epigenomic experiments | |
Cell membrane permeabilization reagent | 11024-24-1 | Digitonin | 50% | Used for cell membrane permeabilization and nuclei processing; suitable for cleavage under targets, tagmentation, and chromatin-related experimental workflows | |
Nucleic acid precipitation aid | 9005-79-2 | Glycogen | ≥85% (dry basis) | Used for low-input nucleic acid precipitation, nucleic acid recovery, and sample processing during sequencing library preparation |
Table 2. Products Related to DNA Methylation, Demethylation, and Methylation Metabolism
Category | CAS No. | Aladdin Cat. No. | Name | Specification or Purity | Product Features and Applications |
Nucleoside DNA methyltransferase inhibitor | 2353-33-5 | 5-Aza-2′-deoxycytidine | Moligand™, ≥98% | Used for DNA hypomethylation, reversal of promoter methylation, and reactivation of methylation-silenced genes | |
Nucleoside DNA methyltransferase inhibitor | 320-67-2 | 5-Azacytidine | Moligand™, ≥98% | Used for DNMT inhibition, DNA hypomethylation, re-expression of methylation-silenced genes, and gene expression remodeling; because it can be incorporated into RNA, RNA-related effects should be considered when interpreting experimental results | |
Nucleoside DNA methyltransferase inhibitor | 929901-49-5 | Guadecitabine | ≥95% | Used for inducing hypomethylation, reactivating methylation-silenced genes, and studying tumor epigenetic regulation | |
Cytidine analog methylation modulator | 3690-10-6 | Zebularine | Moligand™, ≥98% (HPLC) | Used for cytidine analog-mediated inhibition of DNA methylation, gene re-expression, and cell differentiation studies | |
Non-nucleoside DNA methyltransferase inhibitor | 48208-26-0 | RG108, a novel non-nucleoside DNA methyltransferase (DNMT) inhibitor | ≥98% | Used for non-nucleoside inhibition of DNA methyltransferases, methylation-level detection, and transcriptional restoration studies | |
DNA methyltransferase inhibitor | 1020149-73-8 | SGI 1027, DNA methyltransferase inhibitor | Moligand™, ≥98% (HPLC) | Used for inhibition of DNA methyltransferase activity, methylation maintenance studies, and gene expression regulation | |
DNA methylation-related modulator | 51-05-8 | Procaine hydrochloride | Moligand™, ≥99% | Used for DNA methylation regulation, changes in promoter methylation status, and gene expression restoration studies | |
DNA methylation-related modulator | 51-06-9 | 4-Amino-N-(2-diethylaminoethyl)benzamide | Moligand™, ≥97% | Used for studying changes in methylation status, gene expression restoration, and DNA methylation regulation | |
Methylated cytosine standard | 554-01-8 | 5-Methylcytosine | ≥98% | Used for 5-methylcytosine detection, establishment of methylation analysis methods, and quantitative epigenomic studies | |
Hydroxymethylated cytosine standard | 1123-95-1 | 2-Hydroxy-4-amino-5-hydroxymethylpyrimidine (5hmC) | Moligand™, ≥95% | Used for 5-hydroxymethylcytosine detection, analysis of DNA demethylation intermediates, and epigenetic biomarker studies | |
Methyl donor | 29908-03-0 | S-Adenosylmethionine (SAM) | Moligand™, ≥98% | Used for studies of DNA and histone methyltransferase reactions; suitable for methyl donor, one-carbon metabolism, and methyltransferase activity analyses | |
Methyltransferase reaction product | 979-92-0 | S-(5′-Adenosyl)-L-homocysteine (SAH) | Moligand™, ≥98% | Used for feedback regulation of methyltransferase reactions, evaluation of methyltransferase activity, and one-carbon metabolism-related epigenetic studies | |
Dioxygenase cofactor | 328-50-7 | K657647 | α-Ketoglutaric acid | Moligand™, for cell culture, ≥99%, endotoxin ≤10 EU/g, total microbial count ≤100 cfu/g | Used for studies related to TET and Jumonji-family demethylases; suitable for analyzing the relationship between metabolic status and epigenetic regulation |
Dioxygenase activity modulator | 50-81-7 | L-Ascorbic acid | Anhydrous grade, Moligand™, ACS, ≥99% | Used for studies of iron-dependent dioxygenase activity regulation; suitable for experiments related to TET-mediated demethylation and cellular reprogramming | |
Dioxygenase inhibitor | 89464-63-1 | Dimethyloxalylglycine | ≥98% (HPLC) | Used for inhibition studies of α-ketoglutarate-dependent dioxygenases; suitable for experiments related to TET enzymes, Jumonji-family enzymes, and hypoxic responses | |
Mutant isocitrate dehydrogenase 1 inhibitor | 1448347-49-6 | Ivosidenib | Moligand™, ≥98% | Used for studies of mutant isocitrate dehydrogenase 1-associated 2-hydroxyglutarate, abnormal methylation, and differentiation blockade | |
Mutant isocitrate dehydrogenase 2 inhibitor | 1446502-11-9 | Enasidenib | Moligand™, ≥97% | Used for studies of mutant isocitrate dehydrogenase 2-associated metabolic abnormalities, changes in methylation status, and tumor cell differentiation |
Table 3. Products Related to Histone Acetylation Writing, Deacetylation, and Metabolism
Category | CAS No. | Aladdin Cat. No. | Name | Specification or Purity | Product Features and Applications |
p300/CBP acetyltransferase inhibitor | 1889279-16-6 | A-485, p300/CBP inhibitor | Moligand™, ≥98% (HPLC) | Used for inhibition of p300/CBP catalytic activity, histone H3 lysine 27 acetylation, and enhancer activation studies | |
p300/CBP acetyltransferase inhibitor | 328968-36-1 | C646, p300/CBP HAT inhibitor | Moligand™, ≥98% | Used for p300/CBP-related acetyltransferase studies; suitable for experiments on histone acetylation and transcriptional activation regulation | |
Acetyltransferase-related natural product | 16611-84-0 | Anacardic acid | Moligand™, ≥98% | Used for studies related to histone acetylation, transcription factor acetylation, and chromatin activation | |
Acetyltransferase-related natural product | 78824-30-3 | Garcinol | Moligand™, ≥95% | Used for studies of histone acetylation, inflammatory factor expression, and tumor epigenetic regulation | |
Multi-target natural product acetylation modulator | 458-37-7 | Curcumin | Moligand™, natural extract, isomer mixture | Used for natural product research related to histone acetylation, inflammatory transcriptional regulation, and tumor epigenetics | |
Broad-spectrum histone deacetylase inhibitor | 58880-19-6 | Trichostatin A (TSA) | Moligand™, ≥98% | Used for studies of histone hyperacetylation, chromatin opening, and gene expression activation | |
Broad-spectrum histone deacetylase inhibitor | 149647-78-9 | N-Hydroxy-N′-phenyloctanediamide | Moligand™, ≥99% | Used for studies of histone hyperacetylation, chromatin opening, cell-cycle regulation, and tumor epigenetics | |
Broad-spectrum histone deacetylase inhibitor | 404950-80-7 | Panobinostat | Moligand™, ≥98% | Used for multi-subtype histone deacetylase inhibition, histone acetylation accumulation, and tumor cell death studies | |
Histone deacetylase inhibitor | 414864-00-9 | Belinostat (PXD101) | Moligand™, ≥98% | Used for histone deacetylase inhibition, tumor cell differentiation, and transcriptional regulation studies | |
Class I histone deacetylase inhibitor | 209783-80-2 | Entinostat (MS-275) | Moligand™, ≥98% | Used for class I histone deacetylase inhibition, immune regulation, tumor microenvironment studies, and transcriptional remodeling | |
Class I histone deacetylase inhibitor | 726169-73-9 | Mocetinostat (MGCD0103), HDAC inhibitor | Moligand™, ≥98% | Used for class I histone deacetylase inhibition, gene expression remodeling, and tumor cell phenotype studies | |
Histone deacetylase 1/2 inhibitor | 128517-07-7 | Romidepsin, HDAC1 and HDAC2 inhibitor | Moligand™, ≥98% | Used for inhibition of histone deacetylases 1 and 2, enhancement of histone acetylation, and tumor epigenetics studies | |
Histone deacetylase 6 inhibitor | 1252003-15-8 | Tubastatin A | Moligand™, ≥98% | Used for studies of HDAC6-related acetylated tubulin, autophagy, immune regulation, and neuroinflammation | |
Histone deacetylase 8 inhibitor | 950762-95-5 | PCI-34051, HDAC8 inhibitor | ≥98% | Used for studies of histone deacetylase 8 function, cell differentiation, and tumor epigenetics | |
Short-chain fatty acid deacetylase inhibitor | 156-54-7 | Sodium butyrate | BioReagent, ≥99% | Used for enhancement of histone acetylation, studies of gut microbiota metabolite effects, and inflammatory transcriptional regulation | |
Deacetylase-related modulator | 99-66-1 | Valproic acid | Moligand™, ≥98% | Used for studies related to histone deacetylase inhibition, nervous system epigenetics, and gene expression regulation | |
Nicotinamide adenine dinucleotide-dependent deacetylase modulator | 98-92-0 | Nicotinamide | PharmPure™, USP | Used for regulation of nicotinamide adenine dinucleotide-dependent deacetylase activity, metabolic status studies, and chromatin acetylation research | |
Deacetylation reaction cofactor | 53-84-9 | β-Nicotinamide adenine dinucleotide hydrate | Moligand™, for cell culture, ≥96.5% (HPLC), ≥96.5% (spectrophotometric assay), from yeast | Used for nicotinamide adenine dinucleotide-dependent deacetylation reactions, studies of metabolism-epigenetics connections, and cellular energy status | |
SIRT1 inhibitor | 49843-98-3 | 6-Chloro-2,3,4,9-tetrahydro-1H-carbazole-1-carboxamide | Moligand™, ≥98% | Used for studies of SIRT1-related deacetylase activity, metabolic responses, cellular senescence, and inflammatory transcriptional regulation | |
SIRT1/2 inhibitor | 410536-97-9 | Sirtinol | ≥98% | Used for studies of SIRT1/2-related NAD⁺-dependent deacetylase function, cellular senescence, and transcriptional regulation | |
Natural product deacetylation modulator | 501-36-0 | Resveratrol | Moligand™, ≥99% | A multi-target natural product commonly used in studies of metabolic stress, SIRT1-related pathways, cellular senescence, and inflammatory epigenetics; its multi-target effects should be considered when interpreting experimental results |
Table 4. Products Related to Histone Lysine Methyltransferases and Repressive Histone Marks
Category | CAS No. | Aladdin Cat. No. | Name | Specification or Purity | Product Features and Applications |
EZH2 methyltransferase inhibitor | 1403254-99-8 | Tazemetostat (EPZ-6438) | Moligand™, ≥99% | Used for inhibition of EZH2 catalytic activity, reduction of histone H3 lysine 27 trimethylation, and tumor epigenetics studies | |
EZH2 methyltransferase inhibitor | 1396772-26-1 | EPZ005687, EZH2 inhibitor | Moligand™, ≥98% | Used for studies of EZH2-mediated histone H3 lysine 27 trimethylation, Polycomb target genes, and cell differentiation | |
EZH2 methyltransferase inhibitor | 1346574-57-9 | GSK126, EZH2 methyltransferase inhibitor | Moligand™, ≥98% | Used for selective EZH2 inhibition, reduction of histone H3 lysine 27 trimethylation, and tumor cell phenotype studies | |
EZH2 methyltransferase inhibitor | 1346704-33-3 | GSK343, cell-permeable histone H3 lysine 27 (H3K27) methyltransferase EZH2 inhibitor | Moligand™, ≥98% | Used for intracellular EZH2 activity inhibition, histone H3 lysine 27 methylation studies, and repressive chromatin regulation research | |
EZH1/2 methyltransferase inhibitor | 1431612-23-5 | UNC1999, EZH2 methyltransferase inhibitor | Moligand™, ≥98% | Used for studies of EZH1/EZH2-related histone H3 lysine 27 trimethylation and Polycomb complex function | |
EZH2 methyltransferase inhibitor | 1418308-27-6 | EI1, EZH2 inhibitor | Moligand™, ≥96% | Used for PRC2-dependent histone H3 lysine 27 trimethylation, transcriptional repression, and tumor epigenetics studies | |
Methylation metabolism-related modulator | 120964-45-6 | 3-Deazaneplanocin A hydrochloride | Moligand™, ≥99% | Used for studies of S-adenosylhomocysteine hydrolase-related methylation regulation; can indirectly affect PRC2/EZH2, H3K27me3, and gene expression changes | |
DOT1L methyltransferase inhibitor | 1561178-17-3 | SGC 0946, DOT1L inhibitor | Moligand™, ≥99% (HPLC) | Used for studies of histone H3 lysine 79 methylation, transcription elongation, and leukemia epigenetics | |
DOT1L methyltransferase inhibitor | 1338466-77-5 | EPZ 004777, DOT1L inhibitor | Moligand™, ≥98% (HPLC) | Used for studies of histone H3 lysine 79 methylation, HOXA/MEIS1 expression, and mixed-lineage leukemia models | |
DOT1L methyltransferase inhibitor | 1380288-87-8 | Pinometostat (EPZ5676) | Moligand™, ≥98% | Used for studies of DOT1L-mediated histone H3 lysine 79 methylation and leukemia-associated transcriptional programs | |
G9a/GLP methyltransferase inhibitor | 1481677-78-4 | UNC 0642, G9a and GLP inhibitor | Moligand™, ≥99% (HPLC) | Used for studies of histone H3 lysine 9 dimethylation, transcriptional repression, and cell identity regulation | |
G9a/GLP methyltransferase inhibitor | 1527503-11-2 | A 366, G9a/GLP inhibitor | Moligand™, ≥98% (HPLC) | Used for studies of G9a/GLP-mediated histone H3 lysine 9 methylation, chromatin silencing, and transcriptional repression | |
G9a-related methyltransferase inhibitor | 935693-62-2 | BIX-01294, G9a and G9a-like protein histone methyltransferase inhibitor | Moligand™, ≥98% | Used for studies of G9a/G9a-like protein-mediated histone H3 lysine 9 dimethylation and gene silencing | |
G9a/GLP methyltransferase inhibitor | 1255580-76-7 | UNC0638, reversible G9a and GLP histone methyltransferase inhibitor | Moligand™, ≥98% | Used for reversible inhibition of G9a/GLP, histone H3 lysine 9 dimethylation studies, and cell fate regulation | |
SUV39H-related methyltransferase inhibitor | 28097-03-2 | Chaetocin | Moligand™, ≥98% | Used for studies of histone H3 lysine 9 trimethylation, heterochromatin regulation, and oxidative stress-related epigenetics; potential ROS and nonspecific cytotoxic effects should be considered | |
SETD8 methyltransferase inhibitor | 1620401-82-2 | UNC0379 | ≥97% | Used for studies of histone H4 lysine 20 monomethylation, cell cycle, and chromatin structure |
Table 5. Products Related to Protein Arginine Methyltransferases
Category | CAS No. | Aladdin Cat. No. | Name | Specification or Purity | Product Features and Applications |
Protein arginine methyltransferase 5 inhibitor | 1616391-87-7 | EPZ015866 (GSK591), PRMT5/MEP50 complex inhibitor | Moligand™, ≥98% | Used for inhibition of the PRMT5/MEP50 complex, symmetric dimethylarginine modification studies, and tumor cell proliferation research | |
Protein arginine methyltransferase 5 inhibitor | 1616392-22-3 | Pemrametostat (GSK3326595) | ≥98% | Used for studies of PRMT5-mediated arginine methylation, splicing regulation, and tumor epigenetic dependency | |
Type I protein arginine methyltransferase inhibitor | 1831110-54-3 | MS023, cell-active PRMT inhibitor | Moligand™, ≥98% | Used for inhibition of type I protein arginine methyltransferases, asymmetric dimethylarginine modification studies, and transcriptional regulation research | |
Protein arginine methyltransferase 6 inhibitor | 1700663-41-7 | EPZ020411 | Moligand™ | Used for studies of PRMT6-related arginine methylation, chromatin transcriptional regulation, and tumor epigenetics | |
Protein arginine methyltransferase inhibitor | 20324-87-2 | AMI-1, reversible protein arginine methyltransferase inhibitor | ≥98% | Used for inhibition of protein arginine methyltransferase activity, detection of arginine methylation levels, and transcriptional regulation studies |
Table 6. Products Related to Histone Demethylases
Category | CAS No. | Aladdin Cat. No. | Name | Specification or Purity | Product Features and Applications |
H3K27 demethylase inhibitor | 1373422-53-7 | GSK-J1, H3K27 histone demethylase inhibitor | Moligand™, ≥99% | Used for studies of JMJD3/UTX-related histone H3 lysine 27 demethylation, inflammatory gene expression, and cell differentiation | |
Cell-permeable H3K27 demethylase inhibitor | 1373423-53-0 | GSK-J4, cell-permeable JMJD3/UTX histone demethylase inhibitor | Moligand™, ≥98% | Used for intracellular JMJD3/UTX inhibition, regulation of histone H3 lysine 27 trimethylation, and inflammatory transcriptional response studies | |
Lysine-specific demethylase 1 inhibitor | 1431368-48-7 | GSK-LSD1 dihydrochloride | Moligand™, ≥98% | Used for studies of LSD1-mediated demethylation of histone H3 lysine 4 or lysine 9, myeloid differentiation, and tumor epigenetics | |
Lysine-specific demethylase 1 inhibitor | 1423715-09-6 | SP-2509, LSD1 histone demethylase inhibitor | ≥98% | Used for studies of LSD1-related transcriptional complex regulation, tumor cell differentiation, and epigenetic dependency | |
KDM5 demethylase inhibitor | 1628208-23-0 | CPI-455 | ≥98% | Used for studies of KDM5-related regulation of histone H3 lysine 4 trimethylation, drug tolerance, and changes in transcriptional state | |
Jumonji-family histone demethylase inhibitor | 199596-05-9 | JIB-04, Jumonji histone demethylase inhibitor | ≥98% (HPLC) | Used for inhibition of Jumonji-family demethylases, histone methylation balance studies, and tumor transcriptional state research | |
Dioxygenase/demethylase-related inhibitor | 5852-78-8 | 8-Hydroxyquinoline-5-carboxylic acid | Moligand™, ≥97% (HPLC) | Used for studies related to Jumonji-family demethylases and other α-ketoglutarate-dependent oxygenases |
Table 7. Products Related to Epigenetic Reader Proteins, Bromodomains, and Protein Degradation
Category | CAS No. | Aladdin Cat. No. | Name | Specification or Purity | Product Features and Applications |
BET bromodomain inhibitor | 1268524-70-4 | (+)-JQ1, BET bromodomain inhibitor | ≥98% (HPLC) | Used for inhibition of BRD4 binding to acetylated histones, enhancer activation studies, transcription elongation research, and tumor epigenetics | |
BET family bromodomain inhibitor | 1300031-49-5 | I-BET151, isoxazole-based pan-BET family inhibitor | Moligand™, ≥98% | Used for inhibition of BET family proteins, super-enhancer-associated transcription studies, and inflammatory gene expression research | |
BET bromodomain inhibitor | 1260907-17-2 | I-BET762, BRD inhibitor | Moligand™, ≥98% (HPLC) | Used for BET family bromodomain inhibition, BRD4-mediated transcription studies, and tumor epigenetic pharmacology research | |
BET bromodomain inhibitor | 202590-98-5 | OTX015, BET bromodomain inhibitor | Moligand™, ≥98% | Used for BET bromodomain inhibition, MYC-related transcriptional regulation, and tumor cell proliferation studies | |
BET bromodomain inhibitor | 1380087-89-7 | Pelabresib (CPI-0610) | Moligand™, ≥98% | Used for BET protein-mediated transcriptional regulation, enhancer-dependent gene expression, and tumor-related studies | |
BET bromodomain inhibitor | 1403764-72-6 | PFI-1, BET bromodomain inhibitor | Moligand™, ≥98% | Used for functional studies of acetyl-lysine reader proteins; suitable for BRD4-related transcriptional regulation experiments | |
BET bromodomain second-domain-biased inhibitor | 2138861-99-9 | ABBV-744 | Moligand™, ≥99% | Used for studies of the second bromodomain function of BET proteins; suitable for BRD4-related transcriptional regulation, enhancer activation, and tumor dependency analysis | |
BET bromodomain modulator | 1044870-39-4 | Apabetalone | Moligand™, ≥97% | Used for studies of BET bromodomain-related inflammation, lipid metabolism, and vascular gene transcriptional regulation | |
BET protein degrader | 1797406-69-9 | MZ1, (+)-JQ1-based PROTAC that degrades BRD4 | Moligand™, ≥98% | Used for degradation of BRD4 and related BET proteins, studies of chromatin transcriptional program dependency, and protein degradation technology research | |
BET protein degrader | 1950634-92-0 | dBET6 | Moligand™, ≥98% | Used for BET protein degradation, BRD4-dependent transcriptional repression, and chromatin regulation studies | |
BRD9 bromodomain inhibitor | 1714146-59-4 | I-BRD9, BRD9 inhibitor | Moligand™, ≥98% (HPLC) | Used for studies of BRD9-related chromatin remodeling complex function, gene expression regulation, and tumor dependency | |
SWI/SNF-related bromodomain inhibitor | 1819363-80-8 | PFI-3, bromodomain and SMARCA4 inhibitor | Moligand™, ≥98% | Used for studies of SMARCA2/SMARCA4 bromodomain function, chromatin remodeling, and transcriptional regulation | |
BAZ2 bromodomain inhibitor | 1619994-68-1 | GSK2801, BAZ2A and BAZ2B inhibitor | Moligand™, ≥98% (HPLC) | Used for studies of BAZ2A/BAZ2B-related ribosomal DNA chromatin, heterochromatin, and transcriptional repression | |
Broad-spectrum bromodomain inhibitor | 1619994-69-2 | Bromosporine, inhibitor | Moligand™, ≥97% | Used for screening multiple classes of bromodomain reader proteins, acetyl-lysine recognition studies, and epigenetic function research |
Note: The products listed above are representative Aladdin products for scientific research and formulation research. For more information on product specifications, grades, and certificates of analysis (COA), please search by product name, CAS number, or catalog number on the Aladdin website.
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