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Title | CENP-A and CENP-B collaborate to create an open centromeric chromatin state. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 8227, Year 2023 |
Publish date | Dec 12, 2023 |
Authors | Harsh Nagpal / Ahmad Ali-Ahmad / Yasuhiro Hirano / Wei Cai / Mario Halic / Tatsuo Fukagawa / Nikolina Sekulić / Beat Fierz / |
PubMed Abstract | 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 ...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. |
External links | Nat Commun / PubMed:38086807 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.73 - 6.7 Å |
Structure data | EMDB-18699: Human H3 nucleosome assembled on alpha-satellite DNA (Class1: most wrapped DNA) EMDB-18714: Human H3 nucleosome assembled on alpha-satellite DNA (most unwrapped) EMDB-18739: Human CENP-A nucleosome assembled on alpha-satellite DNA (most wrapped DNA) EMDB-18740: Human CENP-A nucleosome assembled on alpha-satellite DNA (partially unwrapped) EMDB-18745: Human Cenp-A nucleosome assembled on alpha-satellite DNA (most unwrapped DNA) EMDB-18753: Human CENP-A nucleosome assembled on alpha-satellite DNA in complex with CENP-B (most wrapped DNA) EMDB-18763: Human CENP-A nucleosome assembled on alpha-satellite DNA in complex with CENP-B (partially unwrapped DNA) EMDB-18768: Human CENP-A nucleosome assembled on alpha-satellite DNA (most unwrapped DNA) EMDB-18775: Human CENP-A nucleosome assembled on 601 DNA with CENP-B box EMDB-18776: Human CENP-A nucleosome assembled on 601 DNA with CENP-B box in complex with CENP-B |
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