Publication Date:
2015-05-09
Description:
Inheritance of each chromosome depends upon its centromere. A histone H3 variant, centromere protein A (CENP-A), is essential for epigenetically marking centromere location. We find that CENP-A is quantitatively retained at the centromere upon which it is initially assembled. CENP-C binds to CENP-A nucleosomes and is a prime candidate to stabilize centromeric chromatin. Using purified components, we find that CENP-C reshapes the octameric histone core of CENP-A nucleosomes, rigidifies both surface and internal nucleosome structure, and modulates terminal DNA to match the loose wrap that is found on native CENP-A nucleosomes at functional human centromeres. Thus, CENP-C affects nucleosome shape and dynamics in a manner analogous to allosteric regulation of enzymes. CENP-C depletion leads to rapid removal of CENP-A from centromeres, indicating their collaboration in maintaining centromere identity.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610723/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4610723/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Falk, Samantha J -- Guo, Lucie Y -- Sekulic, Nikolina -- Smoak, Evan M -- Mani, Tomoyasu -- Logsdon, Glennis A -- Gupta, Kushol -- Jansen, Lars E T -- Van Duyne, Gregory D -- Vinogradov, Sergei A -- Lampson, Michael A -- Black, Ben E -- CA186430/CA/NCI NIH HHS/ -- GM007229/GM/NIGMS NIH HHS/ -- GM008216/GM/NIGMS NIH HHS/ -- GM008275/GM/NIGMS NIH HHS/ -- GM082989/GM/NIGMS NIH HHS/ -- R01 GM082989/GM/NIGMS NIH HHS/ -- T32 GM008216/GM/NIGMS NIH HHS/ -- T32 GM008275/GM/NIGMS NIH HHS/ -- New York, N.Y. -- Science. 2015 May 8;348(6235):699-703. doi: 10.1126/science.1259308.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Graduate Program in Cell and Molecular Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Instituto Gulbenkian de Ciencia, 2780-156 Oeiras, Portugal. ; Graduate Program in Cell and Molecular Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA. ; Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Graduate Program in Cell and Molecular Biology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. Graduate Program in Biochemistry and Molecular Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA. blackbe@mail.med.upenn.edu.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25954010" target="_blank"〉PubMed〈/a〉
Keywords:
Autoantigens/chemistry/genetics/*metabolism
;
Centromere/chemistry/*metabolism/ultrastructure
;
Chromosomal Proteins, Non-Histone/chemistry/genetics/*metabolism
;
DNA/chemistry/metabolism
;
Epigenesis, Genetic
;
Fluorescence Resonance Energy Transfer
;
Gene Knockdown Techniques
;
Humans
;
Nucleosomes/chemistry/*metabolism/ultrastructure
;
Protein Structure, Secondary
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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