Taf7l cooperates with Trf2 to regulate spermiogenesis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 110; no. 42; pp. 16886 - 16891
• Main Authors: Zhou, Haiying, Grubisic, Ivan, Zheng, Ke, He, Ying, Wang, P. Jeremy, Kaplan, Tommy, Tjian, Robert
• Format: Journal Article
• Language: English
• Published: United States NATIONAL ACADEMY OF SCIENCES 15.10.2013; National Acad Sciences; National Academy of Sciences
• Subjects: Animals; Biological Sciences; Female; Gene expression; Gene expression regulation; Gene Expression Regulation - physiology; Genes; Genotype & phenotype; Germ cells; Male; Mating behavior; Mice; Mice, Knockout; Organ Specificity - physiology; RNA polymerase; Rodents; Spermatids; Spermatocytes - cytology; Spermatocytes - metabolism; Spermatogenesis; Spermatogenesis - physiology; Spermatozoa; Spermiogenesis; Stem Cells - cytology; Stem Cells - metabolism; TATA-Binding Protein Associated Factors - genetics; TATA-Binding Protein Associated Factors - metabolism; Telomeric Repeat Binding Protein 2 - genetics; Telomeric Repeat Binding Protein 2 - metabolism; Testes; Testis - metabolism; Tissues; Transcription Factor TFIID - genetics; Transcription Factor TFIID - metabolism; Transcription, Genetic - physiology; contraceptive medicine; RNA-seq; gene regulation; reproduction
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1317034110

TATA-binding protein (TBP)-associated factor 7l (Taf7l; a paralogue of Taf7) and TBP-related factor 2 (Trf2) are components of the core promoter complex required for gene/tissue-specific transcription of protein-coding genes by RNA polymerase II. Previous studies reported that Taf7l knockout (KO) mice exhibit structurally abnormal sperm, reduced sperm count, weakened motility, and compromised fertility. Here we find that continued backcrossing of Taf7l−/Y mice from N5 to N9 produced KO males that are essentially sterile. Genome-wide expression profiling by mRNA-sequencing analysis of wild-type (WT) and Taf7l−/Y (KO) testes revealed that Taf7l ablation impairs the expression of many postmeiotic spermatogenic-specific as well as metabolic genes. Importantly, histological analysis of testes revealed that Taf7l−/Y mice develop postmeiotic arrest at the first stage of spermiogenesis, phenotypically similar to Trf2−/− mice, but distinct from Taf4b−/− mice. Indeed, we find that Taf7l and Trf2 coregulate postmeiotic genes, but none of Taf4b-regulated germ stem cell genes in testes. Genome-wide ChIP-sequencing studies indicate that TAF7L binds to promoters of activated postmeiotic genes in testis. Moreover, biochemical studies show that TAF7L associates with TRF2 both in vitro and in testis, suggesting that TAF7L likely cooperates directly with TRF2 at promoters of a subset of postmeiotic genes to regulate spermiogenesis. Our findings thus provide a previously undescribed mechanism for cell-type–specific transcriptional control involving an interaction between a "nonprototypic" core promoter recognition factor (Trf2) and an orphan TAF subunit (Taf7l) in mammalian testis-specific gene transcription.