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.

中文翻译：

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Basonuclin 1缺乏症会导致睾丸过早老化：BNC1与TAF7L协同调节精子发生。

Basonuclin（BNC1）主要在增殖性角质形成细胞和配子形成细胞中表达。然而，其在精子发生和睾丸衰老中的作用尚不清楚。以前，我们在卵巢早衰家谱中发现了杂合BNC1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逐渐的生育力丧失和睾丸过早衰老。BNC1在小鼠睾丸中的全基因组表达谱分析和直接结合研究（通过染色质免疫沉淀测序）确定了BNC1靶向的几种精子发生特异性基因启动子，包括海胆样家族成员10（Khlh10），睾丸表达14（Tex14）和精子发生和中心相关1（Spatc1）。而且，生化分析表明，BNC1在体外和睾丸中均与TATA-box结合蛋白相关因子7（TAF7L）（转录因子IID TAF7亚基的生殖细胞特异性旁系同源物）相关，这表明BNC1可能与TAF7L调节精子发生。截短突变使BNC1 / TAF7L复合物的核易位失效，从而干扰了相关基因的表达并导致睾丸过早衰老。同样，在男性睾丸中，BNC1，TAF7L，Y盒结合蛋白2（YBX2），精子尾巴1的外致密纤维和3磷酸甘油醛脱氢酶，生精（GAPDHS）的表达明显降低。非阻塞性无精子症。