Epigenetic landscape of synthetic human centromeres: Euchromatic modifications coexist interdependently at CENP-A dense regions and prevent intrusion of other modifications [ChIP-seq]

Human centromere is organized on a portion of homogeneously repeated DNA sequence, and contains nucleosomes including centromere specific histone H3, CENP-A. Histone modifications around the CENP-A dense region are also thought to have important roles in centromere function. Here, we used human artificial chromosome (HAC) technology to create functional centromeric chromatin on a synthetic centromeric repeat DNA sequence that allowed for structural analysis at 2-kb resolution.

Analysis using this HAC centromere showed that the CENP-A dense regions are approximately 18–50 kb in size and coexisted with euchromatic histone modifications in a mutually dependent manner. We also find that when DNA replication reduces CENP-A density, a heterochromatin modification H3K9me3 transiently intrudes CENP-A-dense regions, and that both the CENP-A deposition factor HJURP and the histone acetyltransferase KAT7 are important for pushing back this intrusion.