Ccp1 Homodimer Mediates Chromatin Integrity by Antagonizing CENP-A Loading.
CENP-A is a centromere-specific histone 3 variant essential for centromere specification. CENP-A partially replaces canonical histone H3 at the centromeres. How the particular CENP-A/H3 ratio at centromeres is precisely maintained is unknown. It also remains unclear how CENP-A is excluded from non-centromeric chromatin. Here, we identify Ccp1, an uncharacterized NAP family protein in fission yeast that antagonizes CENP-A loading at both centromeric and non-centromeric regions. Like the CENP-A loading factor HJURP, Ccp1 interacts with CENP-A and is recruited to centromeres at the end of mitosis in a Mis16-dependent manner. These data indicate that factors with opposing CENP-A loading activities are recruited to centromeres. Furthermore, Ccp1 also cooperates with H2A.Z to evict CENP-A assembled in euchromatin. Structural analyses indicate that Ccp1 forms a homodimer that is required for its anti-CENP-A loading activity. Our study establishes mechanisms for maintenance of CENP-A homeostasis at centromeres and the prevention of ectopic assembly of centromeres.
Department of Biology, New York University, New York, NY 10003, USA.
Qianhua
Q
Dong
University of Chinese Academy of Sciences, Beijing 100101, China.
Feng-Xiang
FX
Yin
State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Biomacromolecules, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Feng
F
Gao
Department of Biology, New York University, New York, NY 10003, USA.
Yuan
Y
Shen
University of Chinese Academy of Sciences, Beijing 100101, China.
Faben
F
Zhang
State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Biomacromolecules, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Yang
Y
Li
Department of Biology, New York University, New York, NY 10003, USA.
Haijin
H
He
Department of Biology, New York University, New York, NY 10003, USA.
Marlyn
M
Gonzalez
Department of Biology, New York University, New York, NY 10003, USA.
Jinpu
J
Yang
Department of Biology, New York University, New York, NY 10003, USA.
Shu
S
Zhang
State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Biomacromolecules, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Min
M
Su
State Key Laboratory of Molecular Developmental Biology, CAS Center for Excellence in Biomacromolecules, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100101, China.
Yu-Hang
YH
Chen
Department of Biology, New York University, New York, NY 10003, USA.
Fei
F
Li
D001665:Binding Sites; D002268:Carboxypeptidases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002503:Centromere / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D022041:Euchromatin / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008938:Mitosis; D011485:Protein Binding; D000072756:Protein Conformation, alpha-Helical; D000072757:Protein Conformation, beta-Strand; D054730:Protein Interaction Domains and Motifs; D055503:Protein Multimerization; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism / Q000648:ultrastructure; D029702:Schizosaccharomyces pombe Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
D002352:Carrier Proteins; D002868:Chromosomal Proteins, Non-Histone; C410349:Cnp1 protein, S pombe; D022041:Euchromatin; D006657:Histones; C539322:Mis16 protein, S pombe; D029702:Schizosaccharomyces pombe Proteins; D002268:Carboxypeptidases
J Cell Biol. 2001 Dec 24;155(7):1137-45
11756468
PLoS Genet. 2012 Sep;8(9):e1002985
23028377
J Cell Sci. 2012 Jan 15;125(Pt 2):411-21
22331359
Curr Opin Genet Dev. 2013 Apr;23(2):219-27
23219400
Nature. 1980 Oct 9;287(5782):504-9
6999364
Nucleic Acids Res. 2006;34(21):6247-55
17090596
Cell. 2004 Sep 17;118(6):715-29
15369671
Trends Genet. 2014 Feb;30(2):66-74
24342629
Mol Cell. 2011 Feb 18;41(4):398-408
21329878
Cell Cycle. 2014;13(9):1400-12
24626186
J Biol Chem. 1992 Oct 15;267(29):20980-6
1400414
Curr Biol. 2007 Feb 6;17(3):237-43
17222555
EMBO J. 2011 Jan 19;30(2):233-4
21245889
Elife. 2014 Jul 15;3:e02137
25027692
Dev Cell. 2006 Mar;10(3):303-15
16516834
Chromosome Res. 2012 Jul;20(5):607-19
22723125
Genes Dev. 2014 Aug 15;28(16):1815-26
25128498
Nature. 2011 Apr 14;472(7342):234-7
21412236
Genetics. 2013 Jun;194(2):513-8
23525333
Chromosome Res. 2003;11(4):345-57
12906131
Proc Natl Acad Sci U S A. 2007 Mar 13;104(11):4285-90
17360516
Proc Natl Acad Sci U S A. 2011 Jun 7;108(23):9367-71
21606327
Nat Struct Mol Biol. 2004 Nov;11(11):1076-83
15475964
EMBO J. 2011 Jan 19;30(2):328-40
21157429
Biochim Biophys Acta. 2014 Mar;1839(3):241-50
24316467
Mol Cell. 2003 Jan;11(1):175-87
12535531
Science. 2008 Aug 22;321(5892):1088-91
18719285
Nat Struct Mol Biol. 2013 Dec;20(12):1397-406
24186062
Nat Rev Genet. 2008 Dec;9(12):923-37
19002142
Cell. 2009 May 1;137(3):472-84
19410544
Curr Biol. 2004 Nov 9;14(21):1968-72
15530401
Dev Cell. 2014 Sep 8;30(5):496-508
25203206
Nat Cell Biol. 2006 May;8(5):458-69
16622419
Mol Cell. 2009 Feb 13;33(3):299-311
19217404
Elife. 2014 May 20;3:e02203
24844245
Genetics. 2014 Dec;198(4):1433-46
25298518
Cell. 2009 Sep 18;138(6):1067-82
19766562
Dev Cell. 2015 Jul 6;34(1):73-84
26151904
Mol Cell Biol. 1989 Aug;9(8):3342-9
2552293
Trends Cell Biol. 2006 Feb;16(2):70-8
16412639
Mol Cell. 2014 Feb 20;53(4):631-44
24530302
Proc Natl Acad Sci U S A. 2008 Aug 26;105(34):12206-11
18723682
Nat Struct Mol Biol. 2008 Sep;15(9):957-64
19172749
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1248-53
16432217
Cold Spring Harb Perspect Biol. 2014 Nov 20;7(1):a015818
25414369
Mol Biol Cell. 2008 Feb;19(2):682-90
18077559
Science. 2000 Jun 23;288(5474):2215-9
10864871
J Biol Chem. 2007 Apr 27;282(17):12358-62
17344218
Methods Enzymol. 1991;194:795-823
2005825
Proc Natl Acad Sci U S A. 1991 May 1;88(9):3734-8
2023923
Cell. 2009 May 1;137(3):485-97
19410545
Mol Cell. 2009 Feb 13;33(3):287-98
19217403
Genetics. 2008 May;179(1):263-75
18458100
PLoS One. 2013 Jul 31;8(7):e69673
23936074
Genetics. 2011 Jan;187(1):9-19
20944015
Cell. 2011 Feb 18;144(4):471-9
21335232
Curr Opin Struct Biol. 2008 Jun;18(3):282-9
18534842
Proc Natl Acad Sci U S A. 2006 Feb 28;103(9):3090-3
16492771
Nucleic Acids Res. 2016 Mar 18;44(5):2145-59
26586808
Mol Biol Cell. 2009 Sep;20(18):3986-95
19625449
Dev Cell. 2015 Jan 12;32(1):68-81
25556658