Histone H3 acetylation machinery

The Histone H3 acetylation machinery is a multi-component system of enzymes and proteins that regulates the post-translational acetylation of Histone H3, a critical epigenetic mark for gene activation (Selvi et al., 2013) [1.1.1]. This machinery includes 'writers' such as histone acetyltransferases (HATs; e.g., p300, CBP, GCN5) that add acetyl groups to lysine residues, and 'erasers' such as histone deacetylases (HDACs; e.g., HDAC1, HDAC2, HDAC3) that remove them (MDPI, 2024) [1.1.3]. Additionally, 'reader' proteins containing bromodomains, such as BRD4, recognize these acetylated lysines to recruit transcriptional complexes and RNA polymerase II (NIH, 2024) [1.2.1]. The machinery also plays a vital role in DNA repair and cell cycle progression, ensuring genomic stability and proper cellular differentiation (NIH, 2024) [1.3.2]. Dysregulation of this machinery is frequently observed in various cancers, where it contributes to the silencing of tumor suppressors or the activation of oncogenes, as well as in neurodegenerative and inflammatory diseases (elifesciences.org, 2024) [1.1.2]. Pharmacological targeting of this machinery primarily involves HDAC inhibitors, several of which are FDA-approved for treating T-cell lymphomas and multiple myeloma, while HAT and bromodomain inhibitors are currently being evaluated in clinical trials (patsnap.com, 2024) [1.2.5]. Therapeutic challenges include the lack of isoform specificity for many current inhibitors, leading to significant side effects such as hematological toxicity and gastrointestinal distress (MDPI, 2024) [1.3.3]. Ongoing research focuses on developing highly selective inhibitors and combination therapies to overcome resistance and improve the therapeutic index of drugs targeting these epigenetic regulators (elifesciences.org, 2024) [1.1.4].

Other names

Histone H3 acetylation systemHistone H3 acetylation pathwayH3 acetylation regulatorsEpigenetic H3 acetylation machinery

Inhibition of histone deacetylation, inhibition of histone acetylation, and inhibition of bromodomain-mediated acetyl-lysine recognition.