H3K9me3

H3K9me3 refers to the tri-methylation of lysine 9 on histone H3, a histone modification strongly associated with constitutive heterochromatin and transcriptional repression. In many genomes, the mark is enriched at pericentromeric and other repetitive regions and helps maintain a compact chromatin state that limits inappropriate transcription and recombination.

The mark is read by chromatin proteins with chromodomains, notably HP1 family members, which bind H3K9me3 and recruit additional silencing factors, contributing to heterochromatin spreading and genome stability. Writing of H3K9me3 is carried out by histone methyltransferases such as SUV39H1 and SUV39H2, with SETDB1 providing activity in certain contexts; other enzymes contribute to related H3K9 methylation states. Demethylation is performed by KDM4/JMJD2 family demethylases that can remove methyl groups from H3K9me3 to H3K9me2/1, enabling gene reactivation. The G9a/GLP complex primarily establishes H3K9me1/2 rather than trimethylation, illustrating context-dependent writing.

Biological roles include maintenance of X-chromosome inactivation, imprinting, silencing of transposable elements, and repression of repetitive DNA to preserve genome integrity. H3K9me3 dynamics occur during development and differentiation, and alterations in its distribution or levels have been linked to cancers and neurological disorders, making the mark a focus of epigenetic studies and potential therapeutic targeting.