Histone H3 lysine 14 (H3K14)

Histone H3 lysine 14 (H3K14) is a critical amino acid residue located on the amino-terminal tail of the histone H3 protein, which forms part of the nucleosome core in eukaryotic chromatin. This residue is a major site for post-translational modifications (PTMs), most notably acetylation (H3K14ac), which is strongly associated with transcriptionally active chromatin and the recruitment of the basal transcription machinery (UniProt: P68431). The acetylation state of H3K14 is regulated by the balanced activity of histone acetyltransferases (HATs) such as GCN5 (KAT2A), PCAF, and p300/CBP, and histone deacetylases (HDACs) (PubMed: 22634358). In disease contexts, aberrant H3K14 acetylation is frequently observed in various cancers, where it facilitates the overexpression of oncogenes or the silencing of tumor suppressor genes when improperly regulated (PubMed: 24360341). While H3K14 itself is a residue and not a druggable protein, it serves as the essential substrate or recognition site for several classes of epigenetic drugs. These include HDAC inhibitors that maintain the acetylated state to re-activate silenced genes, and bromodomain inhibitors (such as those targeting BRPF1) that prevent 'reader' proteins from binding to the H3K14ac mark (PubMed: 27072641, PubMed: 26053350). Consequently, monitoring H3K14 modification levels is a valuable biomarker for evaluating the pharmacodynamic effects of epigenetic therapies in clinical development.

Other names

H3K14Lysine 14 of histone H3H3 lysine 14Histone H3K14H3.1K14H3.3K14

Modulation of the modification state of the H3K14 residue via the inhibition of histone acetyltransferases (HATs), histone deacetylases (HDACs), or the blocking of reader proteins containing bromodomains that specifically recognize H3K14 acetylation.