An essential role for a mammalian SWI/SNF chromatin-remodeling complex during male meiosis.
Germ cell development and gametogenesis require genome-wide transitions in epigenetic modifications and chromatin structure. These changes include covalent modifications to the DNA and histones as well as remodeling activities. Here, we explore the role of the mammalian SWI/SNF chromatin-remodeling complex during spermatogenesis using a conditional allele of the ATPase subunit, brahma-related gene 1 (Brg1, or Smarca4). Not only do BRG1 levels peak during the early stages of meiosis, genetic ablation of Brg1 in murine embryonic gonocytes results in arrest during prophase of meiosis I. Coincident with the timing of meiotic arrest, mutant spermatocytes accumulate unrepaired DNA and fail to complete synapsis. Furthermore, mutant spermatocytes show global alterations to histone modifications and chromatin structure indicative of a more heterochromatic genome. Together, these data demonstrate a requirement for BRG1 activity in spermatogenesis, and suggest a role for the mammalian SWI/SNF complex in programmed recombination and repair events that take place during meiosis.
Department of Genetics, Carolina Center for Genome Sciences, Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, NC 27599-7264, USA.
Yuna
Y
Kim
Andrew M
AM
Fedoriw
Terry
T
Magnuson
D000818:Animals; D059447:Cell Cycle Checkpoints; D002454:Cell Differentiation / Q000235:genetics; D049109:Cell Proliferation; D002843:Chromatin / Q000502:physiology; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D004249:DNA Damage; D004265:DNA Helicases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D005854:Germ Cells / Q000378:metabolism; D006657:Histones / Q000235:genetics / Q000378:metabolism; D008297:Male; D008540:Meiosis / Q000235:genetics; D051379:Mice; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D013091:Spermatogenesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*
D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; D009687:Nuclear Proteins; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors; C513194:Smarca4 protein, mouse; D004265:DNA Helicases