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.
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Toshinao
authors.initials: T
authors.lastname: Oyama
authors.affiliation: Department of Biology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka 537-8511, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Sasagawa
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
authors.forename: Shugaku
authors.initials: S
authors.lastname: Takeda
authors.affiliation: Veterinary Biosciences, College of Veterinary Medicine, University of Illinois at Urbana-Champaign, Urbana, IL 61802, USA.
authors.forename: Rex A
authors.initials: RA
authors.lastname: Hess
authors.affiliation: The Wistar Institute, Pennsylvania, PA 19104, USA.
authors.forename: Paul M
authors.initials: PM
authors.lastname: Lieberman
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA.
authors.forename: Emily H
authors.initials: EH
authors.lastname: Cheng
authors.affiliation: Human Oncology and Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA; Department of Medicine, Weill Medical College of Cornell University, New York, NY 10021, USA. Electronic address: hsiehj@mskcc.org.
authors.forename: James J
authors.initials: JJ
authors.lastname: Hsieh
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation; D018507:Gene Expression Regulation, Developmental; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051788:Myeloid-Lymphoid Leukemia Protein / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011479:Protamines / Q000235:genetics; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa; D035341:Telomeric Repeat Binding Protein 2 / Q000235:genetics / Q000378:metabolism*; D035561:Transcription Factor TFIIA / Q000378:metabolism*
chemical_list: D002868:Chromosomal Proteins, Non-Histone; C513176:Prm1 protein, mouse; D011479:Protamines; C534796:TRF2 protein, mouse; D035341:Telomeric Repeat Binding Protein 2; D035561:Transcription Factor TFIIA; C053886:spermatid transition proteins; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase; C497423:Kmt2a protein, mouse; C510860:Kmt2d protein, mouse; D010450:Endopeptidases; C513958:taspase1, mouse