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Publication Abstract from PubMed

Centromeres are defined epigenetically by nucleosomes containing the histone H3 variant CENP-A, upon which the constitutive centromere-associated network of proteins (CCAN) is built. CENP-C is considered to be a central organizer of the CCAN. We provide new molecular insights into the structure of human CENP-A nucleosomes, in isolation and in complex with the CENP-C central region (CENP-C(CR) ), the main CENP-A binding module of human CENP-C. We establish that the short alphaN helix of CENP-A promotes DNA flexibility at the nucleosome ends, independently of the sequence it wraps. Furthermore, we show that, in vitro, two regions of human CENP-C (CENP-C(CR) and CENP-C(motif) ) both bind exclusively to the CENP-A nucleosome. We find CENP-C(CR) to bind with high affinity due to an extended hydrophobic area made up of CENP-A(V) (532) and CENP-A(V) (533) . Importantly, we identify two key conformational changes within the CENP-A nucleosome upon CENP-C binding. First, the loose DNA wrapping of CENP-A nucleosomes is further exacerbated, through destabilization of the H2A C-terminal tail. Second, CENP-C(CR) rigidifies the N-terminal tail of H4 in the conformation favoring H4(K20) monomethylation, essential for a functional centromere.

CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail.,Ali-Ahmad A, Bilokapic S, Schafer IB, Halic M, Sekulic N EMBO Rep. 2019 Oct 4;20(10):e48913. doi: 10.15252/embr.201948913. Epub 2019 Sep, 2. PMID:31475439^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.