Cleavage of TFIIA by taspase1 activates TRF2-specified mammalian male germ cell programs

Toshinao Oyama, Satoru Sasagawa, Shugaku Takeda, Rex A. Hess, Paul M. Lieberman, Emily H. Cheng, James J. Hsieh

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)188-200
Number of pages13
JournalDevelopmental cell
Volume27
Issue number2
DOIs
StatePublished - Oct 28 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Developmental Biology
  • Cell Biology

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