CENP-A and CENP-B collaborate to create an open centromeric chromatin state.

Nagpal H, Ali-Ahmad A, Hirano Y, Cai W, Halic M, Fukagawa T, Sekulić N, Fierz B

Nat Commun 14 (1) 8227 [2023-12-12; online 2023-12-12]

Centromeres are epigenetically defined via the presence of the histone H3 variant CENP-A. Contacting CENP-A nucleosomes, the constitutive centromere associated network (CCAN) and the kinetochore assemble, connecting the centromere to spindle microtubules during cell division. The DNA-binding centromeric protein CENP-B is involved in maintaining centromere stability and, together with CENP-A, shapes the centromeric chromatin state. The nanoscale organization of centromeric chromatin is not well understood. Here, we use single-molecule fluorescence and cryoelectron microscopy (cryoEM) to show that CENP-A incorporation establishes a dynamic and open chromatin state. The increased dynamics of CENP-A chromatin create an opening for CENP-B DNA access. In turn, bound CENP-B further opens the chromatin fiber structure and induces nucleosomal DNA unwrapping. Finally, removal of CENP-A increases CENP-B mobility in cells. Together, our studies show that the two centromere-specific proteins collaborate to reshape chromatin structure, enabling the binding of centromeric factors and establishing a centromeric chromatin state.

Cryo-EM [Service]

PubMed 38086807

DOI 10.1038/s41467-023-43739-5

Crossref 10.1038/s41467-023-43739-5

pmc: PMC10716449
pii: 10.1038/s41467-023-43739-5

Publications 9.5.0