Abstract
Sexual reproduction involves the creation of sex-dependent gametes, oocytes and sperm. In mammals, sexually dimorphic differentiation commences in the primordial germ cells (PGCs) in embryonic gonads; PGCs in ovaries and testes differentiate into meiotic primary oocytes and mitotically quiescent prospermatogonia, respectively. Here, we show that the transition from PGCs to sex-specific germ cells was abrogated in conditional knockout mice carrying a null mutation of Smarcb1 (also known as Snf5) gene, which encodes a core subunit of the SWI/SNF chromatin remodeling complex. In female mutant mice, failure to upregulate meiosis-related genes resulted in impaired meiotic entry and progression, including defects in synapsis formation and DNA double strand break repair. Mutant male mice exhibited delayed mitotic arrest and DNA hypomethylation in retrotransposons and imprinted genes, resulting from aberrant expression of genes related to growth and de novo DNA methylation. Collectively, our results demonstrate that the SWI/SNF complex is required for transcriptional reprogramming in the initiation of sex-dependent differentiation of germ cells.
Highlights
Sexual reproduction involves the creation of sex-dependent gametes, oocytes and sperm
Our results clearly demonstrate that the SWI/SNF complex is required for the transition from sexually undifferentiated primordial germ cells (PGCs) to female or male germ cells
We investigated whether the female germ cells in Snf[5] CKO mice successfully entered meiosis by immunohistochemistry using an antibody against synaptonemal complex protein 3 (SYCP3), which is expressed from the preleptotene to the diplotene stages of meiotic prophase cells (Fig. 1C–E)
Summary
Sexual reproduction involves the creation of sex-dependent gametes, oocytes and sperm. Sexually dimorphic differentiation commences in the primordial germ cells (PGCs) in embryonic gonads; PGCs in ovaries and testes differentiate into meiotic primary oocytes and mitotically quiescent prospermatogonia, respectively. We show that the transition from PGCs to sex-specific germ cells was abrogated in conditional knockout mice carrying a null mutation of Smarcb[1] ( known as Snf5) gene, which encodes a core subunit of the SWI/SNF chromatin remodeling complex. Our results demonstrate that the SWI/SNF complex is required for transcriptional reprogramming in the initiation of sex-dependent differentiation of germ cells. Upon specification from PGCs to oocytes or prospermatogonia, the genes involved in PGC differentiation and pluripotency are downregulated, and sexdependent transcriptional programs are a ctivated[3]. Little is known about the transcriptional mechanisms that initiate and drive sex-dependent differentiation of germ cells. SWI/SNF complexes have been shown to remove PRC1 and PRC2 from promoters with bivalent histone m odifications[22,23,24,25]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
