| 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
The histone H3 variant CENP-A is a crucial epigenetic marker for centromere specification. CENP-A forms a characteristic nucleosome and dictates the higher-order configuration of centromeric chromatin. However, little is known about how the CENP-A nucleosome affects the architecture of centromeric chromatin. In this study, we reconstituted tri-nucleosomes mimicking a centromeric nucleosome arrangement containing the CENP-A nucleosome, and determined their 3D structures by cryoelectron microscopy. The H3-CENP-A-H3 tri-nucleosomes adopt an untwisted architecture, with an outward-facing linker DNA path between nucleosomes. This is distinct from the H3-H3-H3 tri-nucleosome architecture, with an inward-facing DNA path. Intriguingly, the untwisted architecture may allow the CENP-A nucleosome to be exposed to the solvent in the condensed chromatin model. These results provide a structural basis for understanding the 3D configuration of CENP-A-containing chromatin, and may explain how centromeric proteins can specifically target the CENP-A nucleosomes buried in robust amounts of H3 nucleosomes in centromeres.
Cryo-EM Structures of Centromeric Tri-nucleosomes Containing a Central CENP-A Nucleosome.,Takizawa Y, Ho CH, Tachiwana H, Matsunami H, Kobayashi W, Suzuki M, Arimura Y, Hori T, Fukagawa T, Ohi MD, Wolf M, Kurumizaka H Structure. 2019 Nov 7. pii: S0969-2126(19)30357-0. doi:, 10.1016/j.str.2019.10.016. PMID:31711756[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
- ↑ Takizawa Y, Ho CH, Tachiwana H, Matsunami H, Kobayashi W, Suzuki M, Arimura Y, Hori T, Fukagawa T, Ohi MD, Wolf M, Kurumizaka H. Cryo-EM Structures of Centromeric Tri-nucleosomes Containing a Central CENP-A Nucleosome. Structure. 2019 Nov 7. pii: S0969-2126(19)30357-0. doi:, 10.1016/j.str.2019.10.016. PMID:31711756 doi:http://dx.doi.org/10.1016/j.str.2019.10.016
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