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

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, TFIIA?-?, and ALF?-? (TFIIA?). Here, we demonstrate that Taspase1-mediated processing of TFIIA?-? drives mammalian spermatogenesis. Both Taspase1(-/-) and noncleavable TFIIA?-?nc/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.

SUBMITTER: Oyama T 

PROVIDER: S-EPMC3947863 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature