Histone lysine residues

Histone lysine residues are the primary sites for post-translational modifications (PTMs) that constitute the 'histone code,' a critical layer of epigenetic regulation (UniProt P68431). Located predominantly on the N-terminal tails of histone proteins H2A, H2B, H3, and H4, these residues undergo dynamic modifications such as acetylation, methylation, ubiquitination, and sumoylation (NIH, 1.3.1). These chemical marks alter the electrostatic interaction between histones and DNA or serve as docking sites for 'reader' proteins, thereby controlling chromatin accessibility and gene transcription (Abcam, 1.2.5). Dysregulation of the enzymes that add (writers), remove (erasers), or recognize (readers) these lysine modifications is linked to the pathogenesis of various cancers, inflammatory conditions, and neurodegenerative diseases (NIH, 1.1.5). While the residues themselves are structural components and not functional protein targets, they are the focal points for a broad class of epigenetic drugs, including HDAC inhibitors (e.g., Vorinostat) and methyltransferase inhibitors (e.g., Tazemetostat), which aim to restore normal gene expression patterns (MDPI, 1.1.4; NIH, 1.4.2).

Other names

Lysine residues on histone tailsH3K4H3K9H3K27H3K36H3K79H4K20Histone tailsHistone lysine modification sites

Inhibition of histone deacetylases (HDACs), histone methyltransferases (HMTs), or bromodomain-containing reader proteins to modulate the modification state of lysine residues and regulate gene expression.