Sohlh1 is required for synaptonemal complex formation by transcriptionally regulating meiotic genes during spermatogenesis in mice

Mol Reprod Dev. 2019 Mar;86(3):252-264. doi: 10.1002/mrd.23100. Epub 2019 Jan 20.

Abstract

Gonad-specific transcription factor spermatogenesis- and oogenesis-specific helix-loop-helix transcription factor 1 (SOHLH1) plays a key role in the transcriptional regulation of the expression of differentiating spermatogonial genes. However, its role in spermatocytes (meiotic male germ cells) remains largely unknown. In this study, Sohlh1 knockout (KO) male mice displayed meiotic defects at the zygotene stage during spermatogenesis. Microarray analyses identified 66 upregulated genes and 139 downregulated genes in Sohlh1 KO testes compared with those in wild-type testes at postnatal Day 7.5. Among many of the downregulated genes, Sycp1 and Sycp3, which encode synaptonemal complex proteins 1 and 3 (SYCP1 and SYCP3), respectively, were significantly reduced in Sohlh1 knockout mice. Transmission electron microscopy revealed no formation of the synaptonemal complex in Sohlh1 KO spermatocytes. Luciferase reporter and chromatin-immunoprecipitation assays demonstrated that SOHLH1 enhanced the expression of the Sycp1 and Sycp3 genes by binding the -1276, -708, and -94 basepairs (bp) E-boxes upstream of the Sycp1 promoter and the -64 and -43 bp E-boxes upstream of the Sycp3 promoter. Our data suggest that SOHLH1 transcriptionally regulates the expression of many target genes critical for the meiotic phase of spermatogenesis.

Keywords: Sycp1; Sycp3; spermatocytes; synapsis; transcription factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics*
  • Cell Cycle Proteins / biosynthesis*
  • DNA-Binding Proteins / biosynthesis*
  • Male
  • Meiosis / genetics*
  • Mice
  • Mice, Knockout
  • Spermatocytes / cytology
  • Spermatogenesis / genetics*
  • Synaptonemal Complex / genetics*
  • Transcriptional Activation / genetics

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Sohlh1 protein, mouse
  • Sycp1 protein, mouse
  • Sycp3 protein, mouse