Structural highlights
Function
CENPA_HUMAN Histone H3-like variant which exclusively replaces conventional H3 in the nucleosome core of centromeric chromatin at the inner plate of the kinetochore. Required for recruitment and assembly of kinetochore proteins, mitotic progression and chromosome segregation. May serve as an epigenetic mark that propagates centromere identity through replication and cell division. The CENPA-H4 heterotetramer can bind DNA by itself (in vitro).[1] [2]
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.
See Also
References
- ↑ Sekulic N, Bassett EA, Rogers DJ, Black BE. The structure of (CENP-A-H4)(2) reveals physical features that mark centromeres. Nature. 2010 Aug 25. PMID:20739937 doi:10.1038/nature09323
- ↑ Hu H, Liu Y, Wang M, Fang J, Huang H, Yang N, Li Y, Wang J, Yao X, Shi Y, Li G, Xu RM. Structure of a CENP-A-histone H4 heterodimer in complex with chaperone HJURP. Genes Dev. 2011 May 1;25(9):901-6. Epub 2011 Apr 8. PMID:21478274 doi:10.1101/gad.2045111
- ↑ Ali-Ahmad A, Bilokapic S, Schafer IB, Halic M, Sekulic N. CENP-C unwraps the human CENP-A nucleosome through the H2A C-terminal tail. EMBO Rep. 2019 Oct 4;20(10):e48913. doi: 10.15252/embr.201948913. Epub 2019 Sep, 2. PMID:31475439 doi:http://dx.doi.org/10.15252/embr.201948913
