Ben Carty

Boundary issues: SWI/SNF shapes chromatin patterns in and around centromeres Abstract. The SWI/SNF family of chromatin remodelling complexes, comprising BAF, PBAF and ncBAF, is known for their critical roles in regulating chromatin

Some Friday reading...new review in Open Biology where we discuss how SWI/SNF maintains the chromatin environment around centromeres, building on recent work from ourselves and others. Lots of fun putting this together with @alison-harrod.bsky.social and @thedownslab.bsky.social!

Thank you Takashi!!

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

Heterochromatin boundaries maintain centromere position, size and number - Nature Structural & Molecular Biology Carty et al. identify the H3K9 methyltransferases that restrict the size and position of the centromere protein A chromatin domain, maintaining functional centromeres.

Very proud to have our latest work now online in
@natsmb.nature.com. A wonderful team effort across the centromere community, across @jansenlab.bsky.social @naltemose.bsky.social @dfachinetti.bsky.social and Giunta labs. Happy reading! 1/4

www.nature.com/articles/s41...

differential contribution of H3K9 methyltransferases to boundaries at satellites

A new and fascinating story from @bencarty.bsky.social and the group, with crucial help from the teams of @naltemose.bsky.social, Simona Giunta, and @dfachinetti.bsky.social. Many thanks to all for a fantastic collaboration.
www.nature.com/articles/s41...

Chromatin profiling identifies putative dual roles for H3K27me3 in regulating cell type-specific genes and transposable elements in choanoflagellates Nature Communications - Here, the authors investigate chromatin-based gene regulation in the closest relative of animal, choanoflagellates. They uncover a putative dual role for the histone...

Very happy to see our paper published online natcomms.nature.com. Thank you to @wellcometrust.bsky.social for funding this work during my time with @robklose.bsky.social and David Booth! Thanks also to collaborators @garcialabms.bsky.social @alexdemendoza.bsky.social and the other authors!

Congrats Dani, Nick and team!!

A fantastic review of the cell cycle control of centromeres from our lab. Lots learned and many open questions 40 years later!

I am looking for a new postdoc to join the lab. Interested in pluripotency, germ cells, and in investigating these in a genetically tractable cnidarian? Get in touch! We offer a long-term contract, excellent research environment, and a lovely city #Galway. www.urifranklab.org

Fresh of the press! rdcu.be/egmY0 We discovered key chromatin modifications that are heritably maintained through mitotic cell divisions in the absence of continued transcription. These hold a memory of past exposure to interferon-gamma, priming cells for future activation of gene expression.

Unlocking the Pause: A new player in gene transcription A new work from the Klose lab published in the journal Molecular Cell

Research @oxfordbiochemistry.bsky.social @ox.ac.uk supported by the Wellcome Trust (UK) and NIH (USA) reveals essential new player in the process of deciding whether genes should be made or not. Great work @jesskelley.bsky.social
@robklose.bsky.social @edimitrova.bsky.social 👏 bit.ly/202502-klose

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!

Heterochromatin boundaries maintain centromere position, size and number Centromeres are chromosomal loci that ensure proper chromosome segregation by providing a platform for kinetochore assembly and spindle force transduction during cell division. Human centromeres are d...

Why is there only one centromere site? But megabases worth of satellite DNA per chromosome? Something surely keeps it in place! In our latest work, we investigate the role of heterochromatin in maintaining centromere position, size and number! A sky(?)torial.. www.biorxiv.org/content/10.1...

@bencarty.bsky.social and the team did a fantastic job in a wonderful collaboration with @naltemose.bsky.social as well as Dani Fachinetti and Simona Giunta’s teams to help define the molecular basis for maintaining centromeric chromatin size and position. www.biorxiv.org/content/10.1...