Histone H4 acetyl-methyllysine marks accessible chromatin that resists compaction

Specific factors and histone modifications mark these regions and help maintain local accessibility. Here, we examine the genomic landscape of acetyl-methyllysine (Kacme), a recently discovered histone post-translational modification.

Across multiple systems, Kacme is highly enriched at sites of accessible chromatin, including active promoters, enhancers, silencers, and CTCF-binding sites. We find that Kacme is selectively retained at loci that resist condensation during mitosis, marks XIST and escapee regions on the inactive X chromosome in female cells, and demarcates the boundaries of broad heterochromatin domains. Using the KDM6A/6B inhibitor GSK-J4 to elevate H3K27me3 levels, we show that Kacme-marked insulator elements block heterochromatin spreading and protect adjacent genes from transcriptional repression.