Cleavage of TFIIA by Taspase1 activates TRF2-specified mammalian male germ cell programs

Dev Cell. 2013 Oct 28;27(2):188-200. doi: 10.1016/j.devcel.2013.09.025.

Abstract

The evolution of tissue-specific general transcription factors (GTFs), such as testis-specific TBP-related factor 2 (TRF2), enables the spatiotemporal expression of highly specialized genetic programs. Taspase1 is a protease that cleaves nuclear factors MLL1, MLL2, TFIIAα-β, and ALFα-β (TFIIAτ). Here, we demonstrate that Taspase1-mediated processing of TFIIAα-β drives mammalian spermatogenesis. Both Taspase1(-/-) and noncleavable TFIIAα-βnc/nc testes release immature germ cells with impaired transcription of Transition proteins (Tnp) and Protamines (Prm), exhibiting chromatin compaction defects and recapitulating those observed with TRF2(-/-) testes. Although the unprocessed TFIIA still complexes with TRF2, this complex is impaired in targeting and thus activating Tnp1 and Prm1 promoters. The current study presents a paradigm in which a protease (Taspase1) cleaves a ubiquitously expressed GTF (TFIIA) to enable tissue-specific (testis) transcription, meeting the demand for sophisticated regulation of distinct subsets of genes in higher organisms.

Publication types

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

MeSH terms

  • Animals
  • Chromosomal Proteins, Non-Histone / genetics
  • Endopeptidases / genetics
  • Endopeptidases / metabolism*
  • Enzyme Activation
  • Gene Expression Regulation, Developmental
  • Histone-Lysine N-Methyltransferase / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Myeloid-Lymphoid Leukemia Protein / metabolism
  • Promoter Regions, Genetic
  • Protamines / genetics
  • Spermatogenesis / physiology*
  • Spermatozoa
  • Telomeric Repeat Binding Protein 2 / genetics
  • Telomeric Repeat Binding Protein 2 / metabolism*
  • Transcription Factor TFIIA / metabolism*

Substances

  • Chromosomal Proteins, Non-Histone
  • Prm1 protein, mouse
  • Protamines
  • TRF2 protein, mouse
  • Telomeric Repeat Binding Protein 2
  • Transcription Factor TFIIA
  • spermatid transition proteins
  • Myeloid-Lymphoid Leukemia Protein
  • Histone-Lysine N-Methyltransferase
  • Kmt2a protein, mouse
  • Kmt2b protein, mouse
  • Endopeptidases
  • taspase1, mouse