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, 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. Copyright © 2013 Elsevier Inc. All rights reserved.

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Toshinao Oyama, Satoru Sasagawa, Shugaku Takeda, Rex A Hess, Paul M Lieberman, Emily H Cheng, James J Hsieh. Cleavage of TFIIA by Taspase1 activates TRF2-specified mammalian male germ cell programs. Developmental cell. 2013 Oct 28;27(2):188-200

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PMID: 24176642

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