Ccp1 Homodimer Mediates Chromatin Integrity by Antagonizing CENP-A Loading

Qianhua Dong; Feng-Xiang Yin; Feng Gao; Yuan Shen; Faben Zhang; Yang Li; Haijin He; Marlyn Gonzalez; Jinpu Yang; Shu Zhang; Min Su; Yu-Hang Chen; Fei Li

doi:10.1016/j.molcel.2016.08.022

Ccp1 Homodimer Mediates Chromatin Integrity by Antagonizing CENP-A Loading

Mol Cell. 2016 Oct 6;64(1):79-91. doi: 10.1016/j.molcel.2016.08.022. Epub 2016 Sep 22.

Authors

Qianhua Dong^#¹, Feng-Xiang Yin^#², Feng Gao³, Yuan Shen¹, Faben Zhang², Yang Li³, Haijin He¹, Marlyn Gonzalez¹, Jinpu Yang¹, Shu Zhang¹, Min Su³, Yu-Hang Chen³, Fei Li¹

Affiliations

¹ Department of Biology, New York University, New York, NY 10003, USA.
² University of Chinese Academy of Sciences, Beijing 100101, China.
³ 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.

^# Contributed equally.

Abstract

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.

MeSH terms

Binding Sites
Carboxypeptidases / chemistry
Carboxypeptidases / genetics*
Carboxypeptidases / metabolism
Carrier Proteins / chemistry
Carrier Proteins / genetics*
Carrier Proteins / metabolism
Centromere / chemistry
Centromere / metabolism
Centromere / ultrastructure
Chromatin Assembly and Disassembly
Chromosomal Proteins, Non-Histone / chemistry
Chromosomal Proteins, Non-Histone / genetics*
Chromosomal Proteins, Non-Histone / metabolism
Euchromatin / chemistry*
Euchromatin / metabolism
Euchromatin / ultrastructure
Gene Expression Regulation, Fungal*
Histones / chemistry
Histones / genetics
Histones / metabolism
Mitosis
Protein Binding
Protein Conformation, alpha-Helical
Protein Conformation, beta-Strand
Protein Interaction Domains and Motifs
Protein Multimerization
Schizosaccharomyces / genetics*
Schizosaccharomyces / metabolism
Schizosaccharomyces / ultrastructure
Schizosaccharomyces pombe Proteins / chemistry
Schizosaccharomyces pombe Proteins / genetics*
Schizosaccharomyces pombe Proteins / metabolism
Signal Transduction

Substances

Carrier Proteins
Chromosomal Proteins, Non-Histone
Cnp1 protein, S pombe
Euchromatin
Histones
Mis16 protein, S pombe
Schizosaccharomyces pombe Proteins
Carboxypeptidases

Grants and funding

R01 GM106037/GM/NIGMS NIH HHS/United States