Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis

作     者：Jing-Yi Li Yi-Feng Liu Hai-Yan Xu Jun-Yu Zhang Ping-Ping Lv Miao-E Liu Yan-Yun Ying Ye-Qing Qian Kun Li Cheng Li Yun Huang Gu-Feng Xu Guo-Lian Ding Yu-Chan Mao Chen-Ming Xu Xin-Mei Liu Jian-Zhong Sheng Dan Zhang He-Feng Huang Jing-Yi Li;Yi-Feng Liu;Hai-Yan Xu;Jun-Yu Zhang;Ping-Ping Lv;Miao-E Liu;Yan-Yun Ying;Ye-Qing Qian;Kun Li;Cheng Li;Yun Huang;Gu-Feng Xu;Guo-Lian Ding;Yu-Chan Mao;Chen-Ming Xu;Xin-Mei Liu;Jian-Zhong Sheng;Dan Zhang;He-Feng Huang

作者机构：Key Laboratory of Reproductive Genetics(Ministry of Education)and Department of Reproductive EndocrinologyWomen's HospitalZhejiang University School of MedicineHangzhou 310006China International Peace Maternal and Child Health HospitalShanghai Jiao Tong UniversityShanghai 200030China Department of Pathology&PathophysiologyZhejiang University School of MedicineHangzhou 310000China 

出 版 物：《Journal of Molecular Cell Biology》 (分子细胞生物学报（英文版）)

年 卷 期：2020年第12卷第1期

页      面：71-83页

核心收录：

学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学] 

基　　金：This work was supported by the National Key Research and Development Program of China(2018YFC1005003,2017YFC1001003,and 2017YFC1001303) the National Natural Science Foundation of China(81471421,81401219,and 81701461) The Fundamental Research Funds for the Central Universities,Natural Science Foundation of Zhejiang Province(Q19H040040) Key Research Program of Zhejiang Provincial Natural Science Foundation(LZ18H040001) Municipal Human Resources Development Program for Outstanding Young Talents in Medical and Health Sciences in Shanghai(2018YQ39) Zhejiang University Education Foundation Global Partnership Fund 

主　　题：testicular aging spermatogenesis BNC1 TAF7L gene mutation 

摘      要：Basonuclin(BNC1)is expressed primarily in proliferative keratinocytes and gametogenic ***,its roles in spermatogenesis and testicular aging were not *** we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency *** this study,we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature ***-wide expression profiling and direct binding studies(by chromatin immunoprecipitation sequencing)with BNC1 in mouse testis identified several spermatogenesis-specific gene promoters targeted by BNC1 including kelch-like family member 10(Klhl1O),testis expressed 14(Tex14)9 and spermatogenesis and centriole associated 1(Spatcl).Moreover,biochemical analysis showed that BNC1 was associated with TATA-box binding protein-associated factor 7 like(TAF7L),a germ cell-specific paralogue of the transcription factor IID subunit TAF7,both in vitro and in testis,suggesting that BNC1 might directly cooperate with TAF7L to regulate *** truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex,thus,disturbing expression of related genes and leading to testicular premature ***,expressions of Y-box-binding protein 2(YBX2),outer dense fiber of sperm tails 1(ODfl),and glyceraldehyde-3-phosphate dehydrogenase,spermatogenic(GAPDHS)were significantly decreased in the testis of men with non-obstructive *** present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men.