UHRF1 is indispensable for meiotic sex chromosome inactivation and interacts with the DNA damage response pathway in mice†

被引:1
|
作者
Xiong, Mengneng [1 ]
Zhou, Shumin [1 ]
Feng, Shenglei [1 ]
Gui, Yiqian [1 ]
Li, Jinmei [1 ]
Wu, Yanqing [1 ]
Dong, Juan [1 ]
Yuan, Shuiqiao [1 ,2 ,3 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Inst Reprod Hlth, Wuhan 430030, Hubei, Peoples R China
[2] Shenzhen Huazhong Univ Sci & Technol, Res Inst, Shenzhen, Guangdong, Peoples R China
[3] Huazhong Univ Sci & Technol, Lab Anim Ctr, Wuhan, Peoples R China
基金
中国国家自然科学基金;
关键词
DNA damage response; male infertility; meiosis; meiotic sex chromosome inactivation (MSCI); UHRF1; XY BODY; GENE; CHROMATIN; SPERMATOGENESIS; SPERMATOGONIA; ASYNAPSIS; REPAIR; RECOMBINATION; ESTABLISHES; SPERMATIDS;
D O I
10.1093/biolre/ioac054
中图分类号
Q [生物科学];
学科分类号
07 ; 0710 ; 09 ;
摘要
UHRF1 is directly interacts with BRCA1 and has critical role in meiotic sex chromosome inactivation (MSCI). During male meiosis, the constitutively unsynapsed XY chromosomes undergo meiotic sex chromosome inactivation (MSCI), and the DNA damage response (DDR) pathway is critical for MSCI establishment. Our previous study showed that UHRF1 (ubiquitin-like, with PHD and ring finger domains 1) deletion led to meiotic arrest and male infertility; however, the underlying mechanisms of UHRF1 in the regulation of meiosis remain unclear. Here, we report that UHRF1 is required for MSCI and cooperates with the DDR pathway in male meiosis. UHRF1-deficient spermatocytes display aberrant pairing and synapsis of homologous chromosomes during the pachytene stage. In addition, UHRF1 deficiency leads to aberrant recruitment of ATR and FANCD2 on the sex chromosomes and disrupts the diffusion of ATR to the XY chromatin. Furthermore, we show that UHRF1 acts as a cofactor of BRCA1 to facilitate the recruitment of DDR factors onto sex chromosomes for MSCI establishment. Accordingly, deletion of UHRF1 leads to the failure of meiotic silencing on sex chromosomes, resulting in meiotic arrest. In addition to our previous findings, the present study reveals that UHRF1 participates in MSCI, ensuring the progression of male meiosis. This suggests a multifunctional role of UHRF1 in the male germline.
引用
收藏
页码:168 / 182
页数:15
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