Histone Modification Cheatsheet

Key Histone Marks and Their Functions

Histone modifications play crucial roles in regulating chromatin structure and gene expression. This cheatsheet provides a quick reference for the most common and well-characterized histone marks.

Histone Mark	Associated With	Function/Location	Writers	Erasers
H3K4me3	Active promoters	Found near transcription start sites (TSS) of actively transcribed genes. Creates a sharp, localized peak at the 5' end of genes. Provides docking sites for chromatin remodeling complexes.	SET1A/B, MLL1-4	KDM5A-D (JARID1A-D)
H3K27ac	Active enhancers and promoters	Distinguishes active enhancers/promoters from poised ones. Often co-occurs with H3K4me1 at active enhancers. Mutually exclusive with repressive H3K27me3.	CBP, p300	HDAC1, HDAC2, SIRT1
H3K4me1	Poised/primed enhancers	Common at enhancers; alone (without H3K27ac) suggests potential activity but not current activation. More broadly distributed than H3K4me3. Enriched in intergenic regions.	MLL3/4, SET7/9	KDM1A (LSD1), KDM5A-D
H3K27me3	Repression (Polycomb)	Found at silent genes, especially developmental regulators. Mediates repression via Polycomb group proteins. Typically marks temporary silencing during development.	EZH1/2 (PRC2 complex)	KDM6A (UTX), KDM6B (JMJD3)
H3K9me3	Constitutive heterochromatin	Deeply repressive; often near repetitive or structural regions (e.g., centromeres, telomeres). Creates stable, heritable gene silencing. Serves as a docking site for HP1 proteins.	SUV39H1/2, SETDB1, G9a	KDM4A-C (JMJD2A-C)
H3K36me3	Transcribed gene bodies	Marks actively transcribed regions—helps regulate splicing and chromatin compaction. Increases towards the 3' end of genes. Prevents cryptic transcription within gene bodies.	SETD2 (Set2)	KDM4A-C (JMJD2A-C)
H3K9ac	Active chromatin	Associated with transcriptionally active genes. Often co-occurs with H3K4me3 at active promoters. Promotes an open chromatin structure.	GCN5, PCAF, p300/CBP	HDAC1-3, SIRT1, SIRT6

Additional Important Histone Marks

Histone Mark	Associated With	Function/Location
H3K79me2/3	Transcription elongation	Found in gene bodies of actively transcribed genes, enriched near the 5' end. Associated with leukemogenic translocations.
H4K20me1	Transcription regulation	Associated with active transcription. Important for cell cycle progression.
H4K20me3	Heterochromatin	Enriched at constitutive heterochromatin and repetitive elements. Important for genome stability.
H2AK119ub	Gene silencing	Deposited by Polycomb Repressive Complex 1 (PRC1). Works with H3K27me3 in gene silencing.
H3K56ac	DNA repair, replication	Important for nucleosome assembly during DNA replication and repair.

Histone Mark Combinations and Their Significance

Combinations of histone marks create specific "chromatin states" that influence gene expression:

Combination	Significance
H3K4me3 + H3K27me3	"Bivalent domains" - poised/primed developmental genes in stem cells
H3K4me1 + H3K27ac	Active enhancers
H3K4me1 without H3K27ac	Poised/inactive enhancers
H3K4me3 + H3K9ac + H3K27ac	Highly active promoters
H3K9me3 + H4K20me3	Constitutive heterochromatin
H3K36me3 + H3K79me2	Actively transcribed gene bodies

Chromatin States and Gene Activity

Chromatin State	Typical Histone Marks	Gene Activity
Active Promoters	H3K4me3, H3K9ac, H3K27ac	High transcription
Active Enhancers	H3K4me1, H3K27ac	Enhances transcription of target genes
Poised Enhancers	H3K4me1 (without H3K27ac)	Prepared for activation
Polycomb Repressed	H3K27me3, H2AK119ub	Developmental silencing, can be reactivated
Heterochromatin	H3K9me3, H4K20me3	Stably repressed, structural
Transcribed Regions	H3K36me3, H3K79me2	Active elongation

Technical Notes

Histone mark nomenclature: H(histone)(residue position)(modification)
- Example: H3K4me3 = Histone H3, Lysine 4, tri-methylation
Common modifications:
- me1/me2/me3: mono/di/tri-methylation
- ac: acetylation
- ph: phosphorylation
- ub: ubiquitination