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

doi:10.1016/j.devcel.2013.09.025

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

Section of Medical Oncology

Research output: Contribution to journal › Article › peer-review

30 Scopus citations

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 language	English
Pages (from-to)	188-200
Number of pages	13
Journal	Developmental cell
Volume	27
Issue number	2
DOIs	https://doi.org/10.1016/j.devcel.2013.09.025
State	Published - Oct 28 2013

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title = "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, 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.",

author = "Toshinao Oyama and Satoru Sasagawa and Shugaku Takeda and Hess, {Rex A.} and Lieberman, {Paul M.} and Cheng, {Emily H.} and Hsieh, {James J.}",

note = "Funding Information: This work was supported by an NCI Howard Temin Award, R01CA19008 (NIH), and U01CA138505 (NIH) to J.J.H. S.S. was funded by the Japan Society for the Promotion of Science. We thank members of the Cheng and Hsieh laboratories for their insightful comments and Drs. Yuki Okada and Yi Zhang for technical discussions. ",

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T1 - Cleavage of TFIIA by taspase1 activates TRF2-specified mammalian male germ cell programs

AU - Oyama, Toshinao

AU - Sasagawa, Satoru

AU - Takeda, Shugaku

AU - Hess, Rex A.

AU - Lieberman, Paul M.

AU - Cheng, Emily H.

AU - Hsieh, James J.

N1 - Funding Information: This work was supported by an NCI Howard Temin Award, R01CA19008 (NIH), and U01CA138505 (NIH) to J.J.H. S.S. was funded by the Japan Society for the Promotion of Science. We thank members of the Cheng and Hsieh laboratories for their insightful comments and Drs. Yuki Okada and Yi Zhang for technical discussions.

PY - 2013/10/28

Y1 - 2013/10/28

N2 - 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.

AB - 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.

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

Abstract

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