6mup

Structural highlights

Function

[H2A1C_HUMAN] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [CENPC_HUMAN] Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPC recruits DNA methylation and DNMT3B to both centromeric and pericentromeric satellite repeats and regulates the histone code in these regions.^{[1] [2]} [CENPN_HUMAN] Component of the CENPA-NAC (nucleosome-associated) complex, a complex that plays a central role in assembly of kinetochore proteins, mitotic progression and chromosome segregation. The CENPA-NAC complex recruits the CENPA-CAD (nucleosome distal) complex and may be involved in incorporation of newly synthesized CENPA into centromeres. CENPN is the first protein to bind specifically to CENPA nucleosomes and the direct binding of CENPA nucleosomes by CENPN is required for centromere assembly. Required for chromosome congression and efficiently align the chromosomes on a metaphase plate.^{[3] [4] [5] [6]} [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).^{[7] [8]} [H2B2F_HUMAN] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.

References

1. ↑ Gopalakrishnan S, Sullivan BA, Trazzi S, Della Valle G, Robertson KD. DNMT3B interacts with constitutive centromere protein CENP-C to modulate DNA methylation and the histone code at centromeric regions. Hum Mol Genet. 2009 Sep 1;18(17):3178-93. doi: 10.1093/hmg/ddp256. Epub 2009 May , 29. PMID:19482874 doi:http://dx.doi.org/10.1093/hmg/ddp256
2. ↑ Gascoigne KE, Takeuchi K, Suzuki A, Hori T, Fukagawa T, Cheeseman IM. Induced ectopic kinetochore assembly bypasses the requirement for CENP-A nucleosomes. Cell. 2011 Apr 29;145(3):410-22. doi: 10.1016/j.cell.2011.03.031. PMID:21529714 doi:http://dx.doi.org/10.1016/j.cell.2011.03.031
3. ↑ Foltz DR, Jansen LE, Black BE, Bailey AO, Yates JR 3rd, Cleveland DW. The human CENP-A centromeric nucleosome-associated complex. Nat Cell Biol. 2006 May;8(5):458-69. Epub 2006 Apr 16. PMID:16622419 doi:http://dx.doi.org/ncb1397
4. ↑ Izuta H, Ikeno M, Suzuki N, Tomonaga T, Nozaki N, Obuse C, Kisu Y, Goshima N, Nomura F, Nomura N, Yoda K. Comprehensive analysis of the ICEN (Interphase Centromere Complex) components enriched in the CENP-A chromatin of human cells. Genes Cells. 2006 Jun;11(6):673-84. PMID:16716197 doi:http://dx.doi.org/GTC969
5. ↑ McClelland SE, Borusu S, Amaro AC, Winter JR, Belwal M, McAinsh AD, Meraldi P. The CENP-A NAC/CAD kinetochore complex controls chromosome congression and spindle bipolarity. EMBO J. 2007 Dec 12;26(24):5033-47. doi: 10.1038/sj.emboj.7601927. Epub 2007 Nov , 15. PMID:18007590 doi:http://dx.doi.org/10.1038/sj.emboj.7601927
6. ↑ Carroll CW, Silva MC, Godek KM, Jansen LE, Straight AF. Centromere assembly requires the direct recognition of CENP-A nucleosomes by CENP-N. Nat Cell Biol. 2009 Jul;11(7):896-902. doi: 10.1038/ncb1899. Epub 2009 Jun 21. PMID:19543270 doi:http://dx.doi.org/10.1038/ncb1899
7. ↑ 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
8. ↑ 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