Cleavage of TFIIA by Taspase1 Activates TRF2-Specified Mammalian Male Germ Cell Programs

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