Chd5 orchestrates chromatin remodelling during sperm development

Li, W., Wu, J., Kim, S. Y., Zhao, M., Hearn, S. A., Zhang, M. Q., Meistrich, M. L., Mills, A. A. (2014) Chd5 orchestrates chromatin remodelling during sperm development. Nature Communications, 5. p. 3812. ISSN 20411723

URL: http://www.ncbi.nlm.nih.gov/pubmed/24818823
DOI: 10.1038/ncomms4812

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.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > Chd5
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > Chromatin dynamics
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics
CSHL Cancer Center Shared Resources > Animal Services
CSHL Cancer Center Shared Resources > Animal Tissue and Imaging Service
CSHL Cancer Center Shared Resources > Bioinformatics Service
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Functional Genomics and Genetics Service
CSHL Cancer Center Shared Resources > Gene Targeting Service
CSHL Cancer Center Shared Resources > Genetic Screening Service
CSHL Cancer Center Shared Resources > Microscopy Service
CSHL labs > Mills lab
Stanley Institute for Cognitive Genomics
Depositing User: Matt Covey
Date Deposited: 09 Jun 2014 16:31
Last Modified: 06 Nov 2015 20:58
PMCID: PMC4151132
Related URLs:
URI: http://repository.cshl.edu/id/eprint/30285

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