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Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis
Basonuclin (BNC1) is expressed primarily in proliferative keratinocytes and gametogenic cells. However, its roles in spermatogenesis and testicular aging were not clear. Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree. In this study, we...
Autores principales: | , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052986/ https://www.ncbi.nlm.nih.gov/pubmed/31065688 http://dx.doi.org/10.1093/jmcb/mjz035 |
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author | Li, Jing-Yi Liu, Yi-Feng Xu, Hai-Yan Zhang, Jun-Yu Lv, Ping-Ping Liu, Miao-E Ying, Yan-Yun Qian, Ye-Qing Li, Kun Li, Cheng Huang, Yun Xu, Gu-Feng Ding, Guo-Lian Mao, Yu-Chan Xu, Chen-Ming Liu, Xin-Mei Sheng, Jian-Zhong Zhang, Dan Huang, He-Feng |
author_facet | Li, Jing-Yi Liu, Yi-Feng Xu, Hai-Yan Zhang, Jun-Yu Lv, Ping-Ping Liu, Miao-E Ying, Yan-Yun Qian, Ye-Qing Li, Kun Li, Cheng Huang, Yun Xu, Gu-Feng Ding, Guo-Lian Mao, Yu-Chan Xu, Chen-Ming Liu, Xin-Mei Sheng, Jian-Zhong Zhang, Dan Huang, He-Feng |
author_sort | Li, Jing-Yi |
collection | PubMed |
description | Basonuclin (BNC1) is expressed primarily in proliferative keratinocytes and gametogenic cells. However, its roles in spermatogenesis and testicular aging were not clear. Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree. In this study, we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging. Genome-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 (Klhl10), testis expressed 14 (Tex14), and spermatogenesis and centriole associated 1 (Spatc1). 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 spermatogenesis. The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex, thus, disturbing expression of related genes and leading to testicular premature aging. Similarly, expressions of BNC1, TAF7L, Y-box-binding protein 2 (YBX2), outer dense fiber of sperm tails 1 (ODF1), and glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS) were significantly decreased in the testis of men with non-obstructive azoospermia. The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men. |
format | Online Article Text |
id | pubmed-7052986 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-70529862020-03-09 Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis Li, Jing-Yi Liu, Yi-Feng Xu, Hai-Yan Zhang, Jun-Yu Lv, Ping-Ping Liu, Miao-E Ying, Yan-Yun Qian, Ye-Qing Li, Kun Li, Cheng Huang, Yun Xu, Gu-Feng Ding, Guo-Lian Mao, Yu-Chan Xu, Chen-Ming Liu, Xin-Mei Sheng, Jian-Zhong Zhang, Dan Huang, He-Feng J Mol Cell Biol Article Basonuclin (BNC1) is expressed primarily in proliferative keratinocytes and gametogenic cells. However, its roles in spermatogenesis and testicular aging were not clear. Previously we discovered a heterozygous BNC1 truncation mutation in a premature ovarian insufficiency pedigree. In this study, we found that male mice carrying the truncation mutation exhibited progressively fertility loss and testicular premature aging. Genome-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 (Klhl10), testis expressed 14 (Tex14), and spermatogenesis and centriole associated 1 (Spatc1). 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 spermatogenesis. The truncation mutation disabled nuclear translocation of the BNC1/TAF7L complex, thus, disturbing expression of related genes and leading to testicular premature aging. Similarly, expressions of BNC1, TAF7L, Y-box-binding protein 2 (YBX2), outer dense fiber of sperm tails 1 (ODF1), and glyceraldehyde-3-phosphate dehydrogenase, spermatogenic (GAPDHS) were significantly decreased in the testis of men with non-obstructive azoospermia. The present study adds to the understanding of the physiology of male reproductive aging and the mechanism of spermatogenic failure in infertile men. Oxford University Press 2019-11-04 /pmc/articles/PMC7052986/ /pubmed/31065688 http://dx.doi.org/10.1093/jmcb/mjz035 Text en © The Author(s) (2019). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com |
spellingShingle | Article Li, Jing-Yi Liu, Yi-Feng Xu, Hai-Yan Zhang, Jun-Yu Lv, Ping-Ping Liu, Miao-E Ying, Yan-Yun Qian, Ye-Qing Li, Kun Li, Cheng Huang, Yun Xu, Gu-Feng Ding, Guo-Lian Mao, Yu-Chan Xu, Chen-Ming Liu, Xin-Mei Sheng, Jian-Zhong Zhang, Dan Huang, He-Feng Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis |
title | Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis |
title_full | Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis |
title_fullStr | Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis |
title_full_unstemmed | Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis |
title_short | Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis |
title_sort | basonuclin 1 deficiency causes testicular premature aging: bnc1 cooperates with taf7l to regulate spermatogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7052986/ https://www.ncbi.nlm.nih.gov/pubmed/31065688 http://dx.doi.org/10.1093/jmcb/mjz035 |
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