Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis
Basonuclin 1 deficiency causes testicular premature aging: BNC1 cooperates with TAF7L to regulate spermatogenesis
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Basonuclin 1缺乏导致睾丸早衰：BNC1与TAF7L配合调节精子发生
DOI：
10.1093/jmcb/mjz035
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发表时间：
2020-01-01
影响因子：
5.5
通讯作者：
Huang, He-Feng
中科院分区：
文献类型：
--
作者：
Li, Jing-Yi;Liu, Yi-Feng;Huang, He-Feng
基底核蛋白（BNC 1）主要表达于增殖期的角质形成细胞和配子发生细胞。然而，其在精子发生和睾丸老化中的作用尚不清楚。以前我们在一个卵巢功能不全的家系中发现了一个杂合的BNC 1截短突变。在这项研究中，我们发现携带截短突变的雄性小鼠表现出进行性生育能力丧失和睾丸早衰。全基因组表达谱分析和直接结合研究（染色质免疫沉淀测序）与BNC 1在小鼠睾丸中确定了几个精子发生特异性基因启动子BNC 1靶向包括kelch样家族成员10（Klhl 10），睾丸表达14（Tex 14），精子发生和中心粒相关1（Spatc 1）。此外，生化分析表明，BNC 1与TATA盒结合蛋白相关因子7样（TAF 7 L），转录因子IID亚基TAF 7的生殖细胞特异性的parasites，在体外和在睾丸中，这表明BNC 1可能直接与TAF 7 L调节精子发生。该截短突变使BNC 1/TAF 7 L复合物不能核转位，从而干扰相关基因的表达，导致睾丸早衰。与此类似，非梗阻性无精子症患者睾丸中BNC 1、TAF 7 L、Y-box-binding protein 2（YBX 2）、精子尾部外致密纤维1（ODF 1）和生精甘油醛-3-磷酸脱氢酶（GAPDHS）的表达也显著降低。本研究为了解男性生殖衰老的生理学和不育男性生精障碍的机制提供了新的思路。
Abstract 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.