Epigenetic Modifications

Epigenetic Modifications

Epigenetic modifications are chemical changes to histones and DNA that regulate gene expression without altering the DNA sequence. Histone modifications are particularly dynamic and reversible.

Writers, Readers, and Erasers

• Writers: Enzymes that add modifications (HATs add acetyl groups, KMTs add methyl groups)
• Erasers: Enzymes that remove modifications (HDACs remove acetyl, KDMs remove methyl)
• Readers: Proteins that recognize marks (bromodomains bind acetyl-K, chromodomains bind methyl-K)

Key Histone Marks

• H3K4me3: Active promoters (written by MLL/Set1 complexes)
• H3K27me3: Repressed genes (written by PRC2/EZH2)
• H3K9ac: Active transcription (associated with open chromatin)
• H3K27ac: Active enhancers
• H3K9me3: Heterochromatin (constitutive silencing)

Chromatin States

Acetylation neutralizes the positive charge on lysines, weakening histone-DNA interactions and opening chromatin for transcription. Methylation effects depend on the residue: H3K4me3 promotes transcription while H3K27me3 silences genes through Polycomb repression.

Mark Spreading

Some histone modifications can spread along chromatin through reader-writer coupling. For example, HP1 reads H3K9me3 and recruits more SUV39H1 to methylate adjacent histones, enabling heterochromatin spreading.