title: TRF2 is recruited to the pre-initiation complex as a testis-specific subunit of TFIIA/ALF to promote haploid cell gene expression.
abstract: Mammalian genomes encode two genes related to the TATA-box binding protein (TBP), TBP-related factors 2 and 3 (TRF2 and TRF3). Male Trf2(-/-) mice are sterile and characterized by arrested spermatogenesis at the transition from late haploid spermatids to early elongating spermatids. Despite this characterization, the molecular function of murine Trf2 remains poorly characterized and no direct evidence exists to show that it acts as a bona fide chromatin-bound transcription factor. We show here that Trf2 forms a stable complex with TFIIA or the testis expressed paralogue ALF chaperoned in the cytoplasm by heat shock proteins. We demonstrate for the first time that Trf2 is recruited to active haploid cell promoters together with Tbp, Taf7l and RNA polymerase II. RNA-seq analysis identifies a set of genes activated in haploid spermatids during the first wave of spermatogenesis whose expression is down-regulated by Trf2 inactivation. We therefore propose that Trf2 is recruited to the preinitiation complex as a testis-specific subunit of TFIIA/ALF that cooperates with Tbp and Taf7l to promote haploid cell gene expression.
authors: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UDS. 1 Rue Laurent Fries, 67404, Illkirch Cédex France.
authors: Igor
authors: I
authors: Martianov
authors: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UDS. 1 Rue Laurent Fries, 67404, Illkirch Cédex France.
authors: Amandine
authors: A
authors: Velt
authors: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UDS. 1 Rue Laurent Fries, 67404, Illkirch Cédex France.
authors: Guillaume
authors: G
authors: Davidson
authors: The Friedrich Miescher Institute, Maulbeerstrasse 66, 4058, Basel, Switzerland.
authors: Mohamed-Amin
authors: MA
authors: Choukrallah
authors: Department of Functional Genomics and Cancer, Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/UDS. 1 Rue Laurent Fries, 67404, Illkirch Cédex France.
authors: Irwin
authors: I
authors: Davidson
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics*; D006238:Haploidy; D006360:Heat-Shock Proteins / Q000378:metabolism; D008297:Male; D018345:Mice, Knockout; D009928:Organ Specificity; D011401:Promoter Regions, Genetic; D025941:Protein Interaction Mapping; D021381:Protein Transport; D012319:RNA Polymerase II / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D013087:Spermatids / Q000378:metabolism / Q000648:ultrastructure; D013091:Spermatogenesis / Q000235:genetics*; D035182:TATA Box Binding Protein-Like Proteins / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*; D035561:Transcription Factor TFIIA / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: C485619:Gtf2a1lf protein, mouse; D006360:Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D035182:TATA Box Binding Protein-Like Proteins; C000627217:Tbpl1 protein, mouse; D035561:Transcription Factor TFIIA; D014157:Transcription Factors; D012319:RNA Polymerase II