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
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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