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A Heterozygous Truncating Mutation in BNC1 Causes Male Subfertility: BNC1 Cooperates with TAF7L to Regulate Spermatogenesis

47 Pages Posted: 27 Sep 2018

See all articles by Jingyi Li

Jingyi Li

Zhejiang University

Yifeng Liu

Zhejiang University

Haiyan Xu

Zhejiang University

Junyu Zhang

Shanghai Jiao Tong University (SJTU)

Pingping Lv

Zhejiang University - Key Laboratory of Reproductive Genetics (Ministry of Education)

Miaoe Liu

Zhejiang University

Yeqing Qian

Zhejiang University

Kun Li

Zhejiang University

Gufeng Xu

Zhejiang University

Yiqing Wu

Zhejiang University

Yun Huang

Zhejiang University

Cheng Li

Shanghai Jiao Tong University (SJTU)

Guolian Ding

Shanghai Jiao Tong University (SJTU)

Songchang Chen

Shanghai Jiao Tong University (SJTU)

Chenming Xu

Shanghai Jiao Tong University (SJTU)

Yuchan Mao

Zhejiang University

Xinzhu Li

Shanghai Jiao Tong University (SJTU)

Chengliang Zhou

Zhejiang University

Ye Liu

Shanghai Jiao Tong University (SJTU) - International Peace Maternity and Child Health Hospital; Zhejiang University - Key Laboratory of Reproductive Genetics (Ministry of Education)

Xinmei Liu

Shanghai Jiao Tong University (SJTU)

Jianzhong Sheng

Zhejiang University

Danna Zhang

Zhejiang University

Hefeng Huang

Zhejiang University - Key Laboratory of Reproductive Genetics (Ministry of Education); Zhejiang University - Department of Reproductive Endocrinology

More...

Abstract

Basonuclin (BNC1) is expressed primarily in proliferative keratinocytes and gametogenic cells. However, its role in spermatogenesis is not clear. Previously we discovered a heterozygous BNC1 truncating mutation in a premature ovarian insufficiency pedigree. In this study, we found that male mice carrying the truncating mutation exhibited sub-fertility. Genome-wide expression profiling and direct binding studies(ChIP-seq) with BNC1 in mouse testis identified several spermatogenesis specific gene promoters targeted by BNC1 including Klhl10, Tex14, and Spatc1. Moreover, biochemical analysis showed that BNC1 was associated with TAF7L, a germ-cell-specific paralogue of the TFIID subunit TAF7, both in vitro and in testis, suggesting that BNC1 might directly cooperate with TAF7L to regulate spermatogenesis. The truncating mutation disabled nucleal translocation of  the BNC1/TAF7L complex, thus disturbing expression of related genes. Similarly, expressions of BNC1, TAF7L, YBX2, ODF1, and GAPDHS were significantly decreased in the testis of men with NOA.The present study adds to the understanding of the physiology of male reproduction and the mechanism of spermatogenic failure in infertile men.

Funding: This work was supported by National Key Research and Development Program of China (2017YFC1001003), National Key Research and Development Plan 459 (2017YFC1001303), the National Basic Research Program of China (No.2013CB967404), the National Natural Science Foundation of China (No. 81471421, 81270664), The competent department of Science & Technology Project (No. 2017FZA7013) and the Science Foundation for Distinguished Young Scholars of Zhejiang Province (No.LR14H040001).

Declaration of Interest: The authors declare no conflict of interest.

Ethical Approval: The Medical Ethics Committee of Zhejiang University, approved the study protocol.

Keywords: Male subfertility, Spermatogenesis, BNC1, TAF7L, Gene mutation

Suggested Citation

Li, Jingyi and Liu, Yifeng and Xu, Haiyan and Zhang, Junyu and Lv, Pingping and Liu, Miaoe and Qian, Yeqing and Li, Kun and Xu, Gufeng and Wu, Yiqing and Huang, Yun and Li, Cheng and Ding, Guolian and Chen, Songchang and Xu, Chenming and Mao, Yuchan and Li, Xinzhu and Zhou, Chengliang and Liu, Ye and Liu, Xinmei and Sheng, Jianzhong and Zhang, Danna and Huang, Hefeng, A Heterozygous Truncating Mutation in BNC1 Causes Male Subfertility: BNC1 Cooperates with TAF7L to Regulate Spermatogenesis (August 26, 2018). Available at SSRN: https://ssrn.com/abstract=3244812 or http://dx.doi.org/10.2139/ssrn.3244812

Jingyi Li

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Yifeng Liu

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Haiyan Xu

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Junyu Zhang

Shanghai Jiao Tong University (SJTU)

KoGuan Law School
Shanghai 200030, Shanghai 200052
China

Pingping Lv

Zhejiang University - Key Laboratory of Reproductive Genetics (Ministry of Education)

Zhejiang, 310058
China

Miaoe Liu

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Yeqing Qian

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Kun Li

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Gufeng Xu

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Yiqing Wu

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Yun Huang

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Cheng Li

Shanghai Jiao Tong University (SJTU)

KoGuan Law School
Shanghai 200030, Shanghai 200052
China

Guolian Ding

Shanghai Jiao Tong University (SJTU)

KoGuan Law School
Shanghai 200030, Shanghai 200052
China

Songchang Chen

Shanghai Jiao Tong University (SJTU)

KoGuan Law School
Shanghai 200030, Shanghai 200052
China

Chenming Xu

Shanghai Jiao Tong University (SJTU)

KoGuan Law School
Shanghai 200030, Shanghai 200052
China

Yuchan Mao

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Xinzhu Li

Shanghai Jiao Tong University (SJTU)

KoGuan Law School
Shanghai 200030, Shanghai 200052
China

Chengliang Zhou

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Ye Liu

Shanghai Jiao Tong University (SJTU) - International Peace Maternity and Child Health Hospital

1961 Huashan Rd
Shanghai Shi, 200030
China

Zhejiang University - Key Laboratory of Reproductive Genetics (Ministry of Education)

Zhejiang, 310058
China

Xinmei Liu

Shanghai Jiao Tong University (SJTU)

KoGuan Law School
Shanghai 200030, Shanghai 200052
China

Jianzhong Sheng

Zhejiang University

38 Zheda Road
Hangzhou, Zhejiang 310058
China

Danna Zhang

Zhejiang University

No Address Available

Hefeng Huang (Contact Author)

Zhejiang University - Key Laboratory of Reproductive Genetics (Ministry of Education) ( email )

Zhejiang, 310058
China

Zhejiang University - Department of Reproductive Endocrinology

Zhejiang
China

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