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

• Taspase1 cleaves TFIIA is key to mammalian male germ cell transcription programs
• TFIIA noncleavage (nc) results in sperm compaction defects due to low TNPs and PRMs
• Cleaved TFIIA complexes with TRF2 to form testis-specific transcription machinery
• Taspase1−/− and TFIIA nc/nc mice exhibit same testicular defects as TRF2−/− mice

SummaryThe 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.

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