Essential roles of the chromatin remodeling factor BRG1 in spermatogenesis in mice

Biol Reprod. 2012 Jun 22;86(6):186. doi: 10.1095/biolreprod.111.097097. Print 2012 Jun.

Abstract

Mammalian spermatogenesis is a complex process that involves spatiotemporal regulation of gene expression and meiotic recombination, both of which require the modulation of chromatin structure. Proteins important for chromatin regulation during spermatogenesis remain poorly understood. Here we addressed the role of BRG1, the catalytic subunit of the mammalian Swi/Snf-like BAF chromatin-remodeling complex, during spermatogenesis in mice. BRG1 expression is dynamically regulated in the male germline, being weakly detectable in spermatogonia, highly expressed in pachytene spermatocytes, and turned off in maturing round spermatids. This expression pattern overlaps that of Brm, the Brg1 homolog. While Brm knockout males are known to be fertile, germline-specific Brg1 deletion completely arrests spermatogenesis at the midpachytene stage, which is associated with spermatocyte apoptosis and apparently also with impaired homologous recombination and meiotic sex chromosome inactivation. However, Brg1 is dispensable for gammaH2AX formation during meiotic recombination, contrary to its reported role in DNA repair in somatic cells. Our study reveals the essential role of Brg1 in meiosis and underscores the differences in the mechanisms of DNA repair between germ cells and somatic cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Chromatin Assembly and Disassembly
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Gene Deletion
  • Gene Knockout Techniques
  • Histones / metabolism
  • Male
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Pachytene Stage
  • Recombination, Genetic
  • Spermatocytes / metabolism
  • Spermatogenesis*
  • Testis / cytology
  • Testis / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • H2AX protein, mouse
  • Histones
  • Nuclear Proteins
  • Smarca2 protein, mouse
  • Transcription Factors
  • Smarca4 protein, mouse
  • DNA Helicases