Centromere Identity Maintained by Nucleosomes Assembled with Histone H3 Containing the CENP-A Targeting Domain

Ben E. Black; Lars E T Jansen; Paul S. Maddox; Daniel R. Foltz; Arshad B. Desai; Jagesh V. Shah; Don W. Cleveland

doi:10.1016/j.molcel.2006.12.018

Centromere Identity Maintained by Nucleosomes Assembled with Histone H3 Containing the CENP-A Targeting Domain

Ben E. Black^*, Lars E T Jansen, Paul S. Maddox, Daniel R. Foltz, Arshad B. Desai, Jagesh V. Shah, Don W. Cleveland

^*Corresponding author for this work

Biochemistry and Molecular Genetics

Research output: Contribution to journal › Article › peer-review

206 Scopus citations

Abstract

Active centromeres are marked by nucleosomes assembled with CENP-A, a centromere-specific histone H3 variant. The CENP-A centromere targeting domain (CATD), comprised of loop 1 and the α2 helix within the histone fold, is sufficient to target histone H3 to centromeres and to generate the same conformational rigidity to the initial subnucleosomal heterotetramer with histone H4 as does CENP-A. We now show in human cells and in yeast that depletion of CENP-A is lethal, but recruitment of normal levels of kinetochore proteins, centromere-generated mitotic checkpoint signaling, chromosome segregation, and viability can be rescued by histone H3 carrying the CATD. These data offer direct support for centromere identity maintained by a unique nucleosome that serves to distinguish the centromere from the rest of the chromosome.

Original language	English (US)
Pages (from-to)	309-322
Number of pages	14
Journal	Molecular cell
Volume	25
Issue number	2
DOIs	https://doi.org/10.1016/j.molcel.2006.12.018
State	Published - Jan 26 2007

Funding

We thank G. Kops (UCSD) and I. Cheeseman (UCSD) for helpful discussions, R. Tsien (UCSD), K. Yoda (Nagoya), B. Earnshaw (Edinburgh), K. Sullivan (Scripps), B. Weaver (UCSD), R. Kolodner (UCSD), K. Monier (Lyon), and A. De Antoni and A. Musacchio (Milan) for generously providing reagents, and D. Young (UCSD Flow Cytometry) for sorting cells. Some images were acquired at the UCSD Neuroscience Microscope Shared Facility (Supported by National Institute of Neurological Disorders and Stroke). This work was supported by grants from the National Institutes of Health to D.W.C. B.E.B. was supported by a postdoctoral fellowship from the American Cancer Society and a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund, and L.E.T.J. was supported by a postdoctoral fellowship from Philip Morris USA Inc. Salary support for D.W.C. and A.B.D. is provided by the Ludwig Institute for Cancer Research.

Keywords

CELLCYCLE
DNA

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1016/j.molcel.2006.12.018

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title = "Centromere Identity Maintained by Nucleosomes Assembled with Histone H3 Containing the CENP-A Targeting Domain",

abstract = "Active centromeres are marked by nucleosomes assembled with CENP-A, a centromere-specific histone H3 variant. The CENP-A centromere targeting domain (CATD), comprised of loop 1 and the α2 helix within the histone fold, is sufficient to target histone H3 to centromeres and to generate the same conformational rigidity to the initial subnucleosomal heterotetramer with histone H4 as does CENP-A. We now show in human cells and in yeast that depletion of CENP-A is lethal, but recruitment of normal levels of kinetochore proteins, centromere-generated mitotic checkpoint signaling, chromosome segregation, and viability can be rescued by histone H3 carrying the CATD. These data offer direct support for centromere identity maintained by a unique nucleosome that serves to distinguish the centromere from the rest of the chromosome.",

keywords = "CELLCYCLE, DNA",

author = "Black, {Ben E.} and Jansen, {Lars E T} and Maddox, {Paul S.} and Foltz, {Daniel R.} and Desai, {Arshad B.} and Shah, {Jagesh V.} and Cleveland, {Don W.}",

note = "Funding Information: We thank G. Kops (UCSD) and I. Cheeseman (UCSD) for helpful discussions, R. Tsien (UCSD), K. Yoda (Nagoya), B. Earnshaw (Edinburgh), K. Sullivan (Scripps), B. Weaver (UCSD), R. Kolodner (UCSD), K. Monier (Lyon), and A. De Antoni and A. Musacchio (Milan) for generously providing reagents, and D. Young (UCSD Flow Cytometry) for sorting cells. Some images were acquired at the UCSD Neuroscience Microscope Shared Facility (Supported by National Institute of Neurological Disorders and Stroke). This work was supported by grants from the National Institutes of Health to D.W.C. B.E.B. was supported by a postdoctoral fellowship from the American Cancer Society and a Career Award in the Biomedical Sciences from the Burroughs Wellcome Fund, and L.E.T.J. was supported by a postdoctoral fellowship from Philip Morris USA Inc. Salary support for D.W.C. and A.B.D. is provided by the Ludwig Institute for Cancer Research. ",

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doi = "10.1016/j.molcel.2006.12.018",

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AU - Foltz, Daniel R.

AU - Desai, Arshad B.

AU - Shah, Jagesh V.

AU - Cleveland, Don W.

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N2 - Active centromeres are marked by nucleosomes assembled with CENP-A, a centromere-specific histone H3 variant. The CENP-A centromere targeting domain (CATD), comprised of loop 1 and the α2 helix within the histone fold, is sufficient to target histone H3 to centromeres and to generate the same conformational rigidity to the initial subnucleosomal heterotetramer with histone H4 as does CENP-A. We now show in human cells and in yeast that depletion of CENP-A is lethal, but recruitment of normal levels of kinetochore proteins, centromere-generated mitotic checkpoint signaling, chromosome segregation, and viability can be rescued by histone H3 carrying the CATD. These data offer direct support for centromere identity maintained by a unique nucleosome that serves to distinguish the centromere from the rest of the chromosome.

AB - Active centromeres are marked by nucleosomes assembled with CENP-A, a centromere-specific histone H3 variant. The CENP-A centromere targeting domain (CATD), comprised of loop 1 and the α2 helix within the histone fold, is sufficient to target histone H3 to centromeres and to generate the same conformational rigidity to the initial subnucleosomal heterotetramer with histone H4 as does CENP-A. We now show in human cells and in yeast that depletion of CENP-A is lethal, but recruitment of normal levels of kinetochore proteins, centromere-generated mitotic checkpoint signaling, chromosome segregation, and viability can be rescued by histone H3 carrying the CATD. These data offer direct support for centromere identity maintained by a unique nucleosome that serves to distinguish the centromere from the rest of the chromosome.

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Centromere Identity Maintained by Nucleosomes Assembled with Histone H3 Containing the CENP-A Targeting Domain

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