The Germline Linker Histone dBigH1 and the Translational Regulator Bam Form a Repressor Loop Essential for Male Germ Stem Cell Differentiation

Cell Rep. 2017 Dec 12;21(11):3178-3189. doi: 10.1016/j.celrep.2017.11.060.

Abstract

Drosophila spermatogenesis constitutes a paradigmatic system to study maintenance, proliferation, and differentiation of adult stem cell lineages. Each Drosophila testis contains 6-12 germ stem cells (GSCs) that divide asymmetrically to produce gonialblast cells that undergo four transit-amplifying (TA) spermatogonial divisions before entering spermatocyte differentiation. Mechanisms governing these crucial transitions are not fully understood. Here, we report the essential role of the germline linker histone dBigH1 during early spermatogenesis. Our results suggest that dBigH1 is a general silencing factor that represses Bam, a key regulator of spermatogonia proliferation that is silenced in spermatocytes. Reciprocally, Bam represses dBigH1 during TA divisions. This double-repressor mechanism switches dBigH1/Bam expression from off/on in spermatogonia to on/off in spermatocytes, regulating progression into spermatocyte differentiation. dBigH1 is also required for GSC maintenance and differentiation. These results show the critical importance of germline H1s for male GSC lineage differentiation, unveiling a regulatory interaction that couples transcriptional and translational repression.

Keywords: Bam; Drosophila; GSCs; chromatin; dBigH1; linker histone H1; spermatogenesis.

MeSH terms

  • Animals
  • Cell Differentiation
  • Cell Proliferation
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / growth & development
  • Drosophila melanogaster / metabolism
  • Gene Expression Regulation, Developmental*
  • Histones / genetics*
  • Histones / metabolism
  • Male
  • Protein Biosynthesis
  • Signal Transduction
  • Spermatocytes / cytology
  • Spermatocytes / growth & development
  • Spermatocytes / metabolism*
  • Spermatogenesis / genetics*
  • Spermatogonia / cytology
  • Spermatogonia / growth & development
  • Spermatogonia / metabolism*
  • Testis / cytology
  • Testis / growth & development
  • Testis / metabolism
  • Transcription, Genetic

Substances

  • Drosophila Proteins
  • Histones
  • bam protein, Drosophila