Chromatin modifying enzymes

Chromatin modifying enzymes fall into three broad categories, writers, readers and erasers. Writers include the histone methyltransferases, histone acetyltransferases, some kinases and ubiquitin ligases.  Readers include proteins which contain methyllysine recognition motifs such as bromodomains, chromodomains, tudor domains, PHD zinc fingers, PWWP domains and MBT domains.  Erasers include the histone demethylases and histone deacetylases.  These proteins maintain cell identity and regulate processes such as differentiation, development, proliferation and genome integrity through recognition of specific marks - covalent post-translational modifications - on histone proteins and DNA.

At least eight distinct types of modifications are found on histones, including small covalent modifications such as acetylation, methylation, and phosphorylation, the attachment of larger modifiers such as ubiquitination or sumoylation, and ADP ribosylation, and proline isomerization and deimination.

Dysregulated epigenetic control is associated with human disease such as cancer, where cellular and protein abberations are known to affect chromatin structure, gene transcription and cellular pathways. Due to the reversible nature of epigenetic modifications, chromatin regulators are very tractable targets for drug discovery and the development of novel therapeutics. 

Further reading

Keppler and Archer (2008) Chromatin-modifying enzymes as therapeutic targets--Part 1. Expert Opin Ther Targets.12(10) 1301 PMID: 18781828

Keppler and Archer (2008) Chromatin-modifying enzymes as therapeutic targets--Part 2. Expert Opin Ther Targets 12(11) 1457 PMID: 18851700

Siklos and Kubicek (2022) Therapeutic targeting of chromatin: status and opportunities. FEBS J. 289(5) 1276 PMID: 33982887