title: Chd5 orchestrates chromatin remodelling during sperm development.
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.
authors.affiliation: 1] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [2] Molecular and Cellular Biology Program, Stony Brook University, Stony Brook, New York 11794, USA.
authors.forename: Wangzhi
authors.initials: W
authors.lastname: Li
authors.affiliation: 1] Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA [2] Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, New York 11794, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Wu
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Sang-Yong
authors.initials: SY
authors.lastname: Kim
authors.affiliation: Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Stephen A
authors.initials: SA
authors.lastname: Hearn
authors.affiliation: 1] Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Richardson, Texas 75080, USA [2] MOE Key Laboratory of Bioinformatics and Bioinformatics Division, Center for Synthetic and System Biology, TNLIST/Department of Automation, Tsinghua University, Beijing 100084, China.
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Zhang
authors.affiliation: Department of Experimental Radiation Oncology, MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Marvin L
authors.initials: ML
authors.lastname: Meistrich
authors.affiliation: Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724, USA.
authors.forename: Alea A
authors.initials: AA
authors.lastname: Mills
mesh_terms: D000107:Acetylation; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004265:DNA Helicases / Q000235:genetics* / Q000378:metabolism; D004260:DNA Repair; D006657:Histones / Q000378:metabolism; D007248:Infertility, Male / Q000235:genetics* / Q000378:metabolism; D008297:Male; D051379:Mice; D046529:Microscopy, Electron, Transmission; D011479:Protamines / Q000378:metabolism; D013091:Spermatogenesis / Q000235:genetics*; D013094:Spermatozoa / Q000378:metabolism*; D013737:Testis / Q000378:metabolism
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D011479:Protamines; C053886:spermatid transition proteins; D004265:DNA Helicases; C583981:Chd5 protein, mouse