Chd5 orchestrates chromatin remodelling during sperm development

Wangzhi Li, Jie Wu, Sang-Yong Kim, Ming Zhao, Stephen A. Hearn, Michael Q. Zhang, Marvin L. Meistrich and Alea A. Mills ()
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Wangzhi Li: Cold Spring Harbor Laboratory
Jie Wu: Cold Spring Harbor Laboratory
Sang-Yong Kim: Cold Spring Harbor Laboratory
Ming Zhao: MD Anderson Cancer Center
Stephen A. Hearn: Cold Spring Harbor Laboratory
Michael Q. Zhang: Center for Systems Biology, The University of Texas at Dallas
Marvin L. Meistrich: MD Anderson Cancer Center
Alea A. Mills: Cold Spring Harbor Laboratory

Nature Communications, 2014, vol. 5, issue 1, 1-15

Abstract: Abstract One of the most remarkable chromatin remodelling processes occurs during spermiogenesis, the post-meiotic phase of sperm development during which histones are replaced with sperm-specific protamines to repackage the genome into the highly compact chromatin structure of mature sperm. Here we identify Chromodomain helicase DNA binding protein 5 (Chd5) as a master regulator of the histone-to-protamine chromatin remodelling process. Chd5 deficiency leads to defective sperm chromatin compaction and male infertility in mice, mirroring the observation of low CHD5 expression in testes of infertile men. Chd5 orchestrates a cascade of molecular events required for histone removal and replacement, including histone 4 (H4) hyperacetylation, histone variant expression, nucleosome eviction and DNA damage repair. Chd5 deficiency also perturbs expression of transition proteins (Tnp1/Tnp2) and protamines (Prm1/2). These findings define Chd5 as a multi-faceted mediator of histone-to-protamine replacement and depict the cascade of molecular events underlying this process of extensive chromatin remodelling.

Date: 2014
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DOI: 10.1038/ncomms4812

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