PHB regulates meiotic recombination via JAK2-mediated histone modifications in spermatogenesis.

Autor:	Zhang LF; Department of Anatomy, Histology & Embryology, Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China., Tan-Tai WJ; Department of Anatomy, Histology & Embryology, Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China., Li XH; Department of Anatomy, Histology & Embryology, Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China., Liu MF; State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences-University of Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, Shanghai Tech University, Shanghai 201210, China., Shi HJ; Key Lab of Reproduction Regulation of NPFPC-Shanghai Institute of Planned Parenthood Research, Fudan University Reproduction and DevelopmentInstitution, Shanghai 200032, China., Martin-DeLeon PA; Department of Biological Sciences, University of Delaware, Newark, DE 19716-2590, USA., O WS; School of Biomedical Sciences, The University of Hong Kong, Hong Kong SAR, P. R. China., Chen H; Department of Anatomy, Histology & Embryology, Key Laboratory of Medical Imaging Computing and Computer Assisted Intervention of Shanghai, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2020 May 21; Vol. 48 (9), pp. 4780-4796.
DOI:	10.1093/nar/gkaa203
Abstrakt:	Previously, we have shown that human sperm Prohibitin (PHB) expression is significantly negatively correlated with mitochondrial ROS levels but positively correlated with mitochondrial membrane potential and motility. However, the possible role of PHB in mammalian spermatogenesis has not been investigated. Here we document the presence of PHB in spermatocytes and its functional roles in meiosis by generating the first male germ cell-specific Phb-cKO mouse. Loss of PHB in spermatocytes resulted in complete male infertility, associated with not only meiotic pachytene arrest with accompanying apoptosis, but also apoptosis resulting from mitochondrial morphology and function impairment. Our mechanistic studies show that PHB in spermatocytes regulates the expression of STAG3, a key component of the meiotic cohesin complex, via a non-canonical JAK/STAT pathway, and consequently promotes meiotic DSB repair and homologous recombination. Furthermore, the PHB/JAK2 axis was found as a novel mechanism in the maintenance of stabilization of meiotic STAG3 cohesin complex and the modulation of heterochromatin formation in spermatocytes during meiosis. The observed JAK2-mediated epigenetic changes in histone modifications, reflected in a reduction of histone 3 tyrosine 41 phosphorylation (H3Y41ph) and a retention of H3K9me3 at the Stag3 locus, could be responsible for Stag3 dysregulation in spermatocytes with the loss of PHB. (© The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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