TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression

Sci Rep. 2016 Aug 31;6:32069. doi: 10.1038/srep32069.

Abstract

Mammalian genomes encode two genes related to the TATA-box binding protein (TBP), TBP-related factors 2 and 3 (TRF2 and TRF3). Male Trf2(-/-) mice are sterile and characterized by arrested spermatogenesis at the transition from late haploid spermatids to early elongating spermatids. Despite this characterization, the molecular function of murine Trf2 remains poorly characterized and no direct evidence exists to show that it acts as a bona fide chromatin-bound transcription factor. We show here that Trf2 forms a stable complex with TFIIA or the testis expressed paralogue ALF chaperoned in the cytoplasm by heat shock proteins. We demonstrate for the first time that Trf2 is recruited to active haploid cell promoters together with Tbp, Taf7l and RNA polymerase II. RNA-seq analysis identifies a set of genes activated in haploid spermatids during the first wave of spermatogenesis whose expression is down-regulated by Trf2 inactivation. We therefore propose that Trf2 is recruited to the preinitiation complex as a testis-specific subunit of TFIIA/ALF that cooperates with Tbp and Taf7l to promote haploid cell gene expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Nucleus / metabolism
  • Cytoplasm / metabolism
  • Gene Expression Regulation / genetics*
  • Haploidy
  • Heat-Shock Proteins / metabolism
  • Male
  • Mice, Knockout
  • Organ Specificity
  • Promoter Regions, Genetic
  • Protein Interaction Mapping
  • Protein Transport
  • RNA Polymerase II / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Spermatids / metabolism
  • Spermatids / ultrastructure
  • Spermatogenesis / genetics*
  • TATA Box Binding Protein-Like Proteins / genetics
  • TATA Box Binding Protein-Like Proteins / metabolism*
  • Testis / metabolism*
  • Transcription Factor TFIIA / metabolism*
  • Transcription Factors / metabolism*

Substances

  • Gtf2a1lf protein, mouse
  • Heat-Shock Proteins
  • Recombinant Fusion Proteins
  • TATA Box Binding Protein-Like Proteins
  • Tbpl1 protein, mouse
  • Transcription Factor TFIIA
  • Transcription Factors
  • RNA Polymerase II