ZFP628 Is a TAF4b-Interacting Transcription Factor Required for Mouse Spermiogenesis
Autor: | Gustafson, Eric A., Seymour, Kimberly A., Sigrist, Kirsten, Rooij, Dirk G. D. E., Freiman, Richard N., Developmental Biology, Sub Developmental Biology |
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Přispěvatelé: | Amsterdam Reproduction & Development (AR&D), Center for Reproductive Medicine, Developmental Biology, Sub Developmental Biology |
Rok vydání: | 2020 |
Předmět: |
Male
Chromosomal Proteins Non-Histone Spermiogenesis Apoptosis ZFP628 male fertility Mice TAF4b 0302 clinical medicine Transcription (biology) Testis Transcriptional regulation meiosis Protamines Mice Knockout 0303 health sciences TFIID Cell biology DNA-Binding Proteins Meiosis medicine.anatomical_structure Male fertility Female Transcription factor II D transcription Transcription Germ cell Research Article Transcriptional Activation Protein subunit Biology Cell Line 03 medical and health sciences Protein Domains Two-Hybrid System Techniques medicine Animals Humans Spermatogenesis Molecular Biology Transcription factor Infertility Male 030304 developmental biology TATA-Binding Protein Associated Factors Spermatid Ovary Cell Biology spermatogenesis spermiogenesis Mice Inbred C57BL HEK293 Cells Transcription Factor TFIID CRISPR-Cas Systems 030217 neurology & neurosurgery Transcription Factors |
Zdroj: | Molecular and Cellular Biology, 40(7). American Society for Microbiology Molecular and cellular biology, 94(7):e00228-19. American Society for Microbiology Mol Cell Biol |
ISSN: | 1098-5549 0270-7306 |
Popis: | TAF4b is a subunit of the TFIID complex that is highly expressed in the ovary and testis and required for mouse fertility. TAF4b-deficient male mice undergo a complex series of developmental defects that result in the inability to maintain long-term spermatogenesis. To decipher the transcriptional mechanisms upon which TAF4b functions in spermatogenesis, we used two-hybrid screening to identify a novel TAF4b-interacting transcriptional cofactor, ZFP628. Deletion analysis of both proteins reveals discrete and novel domains of ZFP628 and TAF4b protein that function to bridge their direct interaction in vitro. Moreover, coimmunoprecipitation of ZFP628 and TAF4b proteins in testis-derived protein extracts supports their endogenous association. Using CRISPR-Cas9, we disrupted the expression of ZFP628 in the mouse and uncovered a postmeiotic germ cell arrest at the round spermatid stage in the seminiferous tubules of the testis in ZFP628-deficient mice that results in male infertility. Coincident with round spermatid arrest, we find reduced mRNA expression of transition protein (Tnp1 and Tnp2) and protamine (Prm1 and Prm2) genes, which are critical for the specialized maturation of haploid male germ cells called spermiogenesis. These data delineate a novel association of two transcription factors, TAF4b and ZFP628, and identify ZFP628 as a novel transcriptional regulator of stage-specific spermiogenesis. |
Databáze: | OpenAIRE |
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