Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A - PubMed (original) (raw)
. 2001 Oct;114(Pt 19):3529-42.
doi: 10.1242/jcs.114.19.3529.
Affiliations
- PMID: 11682612
- DOI: 10.1242/jcs.114.19.3529
Specification of kinetochore-forming chromatin by the histone H3 variant CENP-A
A A Van Hooser et al. J Cell Sci. 2001 Oct.
Abstract
The mechanisms that specify precisely where mammalian kinetochores form within arrays of centromeric heterochromatin remain largely unknown. Localization of CENP-A exclusively beneath kinetochore plates suggests that this distinctive histone might direct kinetochore formation by altering the structure of heterochromatin within a sub-region of the centromere. To test this hypothesis, we experimentally mistargeted CENP-A to non-centromeric regions of chromatin and determined whether other centromere-kinetochore components were recruited. CENP-A-containing non-centromeric chromatin assembles a subset of centromere-kinetochore components, including CENP-C, hSMC1, and HZwint-1 by a mechanism that requires the unique CENP-A N-terminal tail. The sequence-specific DNA-binding protein CENP-B and the microtubule-associated proteins CENP-E and HZW10 were not recruited, and neocentromeric activity was not detected. Experimental mistargeting of CENP-A to inactive centromeres or to acentric double-minute chromosomes was also not sufficient to assemble complete kinetochore activity. The recruitment of centromere-kinetochore proteins to chromatin appears to be a unique function of CENP-A, as the mistargeting of other components was not sufficient for assembly of the same complex. Our results indicate at least two distinct steps in kinetochore assembly: (1) precise targeting of CENP-A, which is sufficient to assemble components of a centromere-prekinetochore scaffold; and (2) targeting of kinetochore microtubule-associated proteins by an additional mechanism present only at active centromeres.
Similar articles
- In vitro centromere and kinetochore assembly on defined chromatin templates.
Guse A, Carroll CW, Moree B, Fuller CJ, Straight AF. Guse A, et al. Nature. 2011 Aug 28;477(7364):354-8. doi: 10.1038/nature10379. Nature. 2011. PMID: 21874020 Free PMC article. - Human CENP-H multimers colocalize with CENP-A and CENP-C at active centromere--kinetochore complexes.
Sugata N, Li S, Earnshaw WC, Yen TJ, Yoda K, Masumoto H, Munekata E, Warburton PE, Todokoro K. Sugata N, et al. Hum Mol Genet. 2000 Nov 22;9(19):2919-26. doi: 10.1093/hmg/9.19.2919. Hum Mol Genet. 2000. PMID: 11092768 - Immunolocalization of CENP-A suggests a distinct nucleosome structure at the inner kinetochore plate of active centromeres.
Warburton PE, Cooke CA, Bourassa S, Vafa O, Sullivan BA, Stetten G, Gimelli G, Warburton D, Tyler-Smith C, Sullivan KF, Poirier GG, Earnshaw WC. Warburton PE, et al. Curr Biol. 1997 Nov 1;7(11):901-4. doi: 10.1016/s0960-9822(06)00382-4. Curr Biol. 1997. PMID: 9382805 - Putting CENP-A in its place.
Stellfox ME, Bailey AO, Foltz DR. Stellfox ME, et al. Cell Mol Life Sci. 2013 Feb;70(3):387-406. doi: 10.1007/s00018-012-1048-8. Epub 2012 Jun 23. Cell Mol Life Sci. 2013. PMID: 22729156 Free PMC article. Review. - Conserved and divergent mechanisms of inner kinetochore assembly onto centromeric chromatin.
Yatskevich S, Barford D, Muir KW. Yatskevich S, et al. Curr Opin Struct Biol. 2023 Aug;81:102638. doi: 10.1016/j.sbi.2023.102638. Epub 2023 Jun 20. Curr Opin Struct Biol. 2023. PMID: 37343495 Review.
Cited by
- Regulation of outer kinetochore assembly during meiosis I and II by CENP-A and KNL-2/M18BP1 in C. elegans oocytes.
Bellutti L, Macaisne N, El Mossadeq L, Ganeswaran T, Canman JC, Dumont J. Bellutti L, et al. Curr Biol. 2024 Nov 4;34(21):4853-4868.e6. doi: 10.1016/j.cub.2024.09.004. Epub 2024 Sep 30. Curr Biol. 2024. PMID: 39353426 - Kinetochore assembly: if you build it, they will come.
Gascoigne KE, Cheeseman IM. Gascoigne KE, et al. Curr Opin Cell Biol. 2011 Feb;23(1):102-8. doi: 10.1016/j.ceb.2010.07.007. Epub 2010 Aug 9. Curr Opin Cell Biol. 2011. PMID: 20702077 Free PMC article. Review. - Histone H1 is essential for mitotic chromosome architecture and segregation in Xenopus laevis egg extracts.
Maresca TJ, Freedman BS, Heald R. Maresca TJ, et al. J Cell Biol. 2005 Jun 20;169(6):859-69. doi: 10.1083/jcb.200503031. J Cell Biol. 2005. PMID: 15967810 Free PMC article. - Inner centromere formation requires hMis14, a trident kinetochore protein that specifically recruits HP1 to human chromosomes.
Kiyomitsu T, Iwasaki O, Obuse C, Yanagida M. Kiyomitsu T, et al. J Cell Biol. 2010 Mar 22;188(6):791-807. doi: 10.1083/jcb.200908096. Epub 2010 Mar 15. J Cell Biol. 2010. PMID: 20231385 Free PMC article. - The histone fold domain of Cse4 is sufficient for CEN targeting and propagation of active centromeres in budding yeast.
Morey L, Barnes K, Chen Y, Fitzgerald-Hayes M, Baker RE. Morey L, et al. Eukaryot Cell. 2004 Dec;3(6):1533-43. doi: 10.1128/EC.3.6.1533-1543.2004. Eukaryot Cell. 2004. PMID: 15590827 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
- CA41424/CA/NCI NIH HHS/United States
- GM39068/GM/NIGMS NIH HHS/United States
- GM48430/GM/NIGMS NIH HHS/United States
- CA64255/CA/NCI NIH HHS/United States
- GM59150/GM/NIGMS NIH HHS/United States
- GM44762/GM/NIGMS NIH HHS/United States
- 073915/Wellcome Trust/United Kingdom
LinkOut - more resources
Full Text Sources
Molecular Biology Databases