Heterochromatin plays a key role in restricting the position of the CENP-A/C domain, ensuring only one CENP-A is nucleated per centromere. SUV39H1/2 and SETDB1 H3K9me3 methyltransferases differentially control neocentromeres, pericentromeric, and core alpha satellites. 4/4

We discover that CENP-A chromatin at a de novo human neocentromere and at canonical alpha satellites are highly plastic! And are surrounded by dense regions of H3K9me3 heterochromatin (& DNAme)! But is this functional? 3/4

With new developments in single molecule epigenomics using @nanoporetech.com, we revisited a key question in chromosome biology - why does pericentric heterochromatin surround the centromere? We hypothesised that it may be required to keep an epigenetic centromere locus in place! 2/4

Congrats Dani, Nick and team!!

This was a very collegial and great collaboration between @jansenlab.bsky.social @naltemose.bsky.social fachinetti and Giunta Labs, which exemplifies what's great about our centromere community. Stay tuned!

But what about the rest of the alpha satellites? To our surprise, we nucleate new centromeres on satellite arrays when we reduce H3K9me3 repressive chromatin. New CDRs, and what appear to be functional dicentrics on mitotic chromosomes!

But does this matter? Absolutely YES. Centromeres move and expand, sometimes quite dramatically.

But how is H3K9me3 being regulated at centromeres? We find roles for SETDB1, SUV39 H1/H2, as well as non-canonical roles for PRC2 component SUZ12! Disruption has a substantial effect on H3K9me3 boundaries

So what about canonical centromeres? First, we find that the active centromere locus contains a distinct dip in H3K9me3, analogous to 5mCG Centromere Dip Regions!

Neo4p13 formed in a SUV39 regulated H3K9me3 domain. We perturbed H3K9me3 and (compensating) H3K27me3 surrounding this centromere.. with some quite dramatic effects on the neocentromere!

How can we model centromere position and inheritence? Using our neocentromere in RPE1 cells (Neo4p13).. we assess centromere position over 100 days of culture. It moves.. somewhat.. but overall size is remarkably consistent!