Reynard Louise N, Cocquet Julie, Burgoyne Paul S
Division of Developmental Genetics and Stem Cell Biology, Medical Research Council National Institute for Medical Research, London, United Kingdom.
Biol Reprod. 2009 Aug;81(2):250-7. doi: 10.1095/biolreprod.108.075382. Epub 2009 Jan 28.
Deletion analysis has established that genes on the Y chromosome are essential for normal sperm production in humans, mice, and Drosophila. In mice, long-arm deletions have an impact on spermiogenesis, with the most extensive deletions resulting in severe sperm head malformations and infertility. Intriguingly, smaller deletions are compatible with fertility but result in a distorted sex ratio in favor of females, and recently it was found that Y long-arm deletions are also associated with a marked upregulation of several X-encoded and Y-encoded spermatid-expressed genes. The mouse Y long arm encodes a number of distinct transcripts, each of which derives from multiple gene copies. Of these multicopy genes, the recently described Sly has been favored as the gene underlying the spermiogenic defects associated with Y long-arm deletions. To assess the candidacy of Sly, the expression of this gene was examined in the testis at the transcript and protein levels. Sly is transcribed after the first meiotic division in secondary spermatocytes and round spermatids and encodes two transcript variants, Sly_v1 and Sly_v2 (proteins referred to as SLY1 and SLY2). We raised an antibody against SLY1 which detected the protein in round and early elongating spermatids, where it is predominantly cytoplasmic. Yeast two-hybrid and coimmunoprecipitation studies demonstrated that SLY1 interacts with the acrosomal protein DKKL1, the histone acetyltransferase KAT5 (also known as TIP60), and the microtubule-associated protein APPBP2. Together, these data suggest SLY1 may be involved in multiple processes during spermiogenesis, including the control of gene expression and the development or function of the acrosome.
缺失分析已证实,Y染色体上的基因对于人类、小鼠和果蝇的正常精子生成至关重要。在小鼠中,长臂缺失会影响精子发生,缺失范围最广时会导致严重的精子头部畸形和不育。有趣的是,较小的缺失与生育能力兼容,但会导致性别比例偏向雌性,最近还发现Y长臂缺失也与多个X编码和Y编码的精子细胞表达基因的显著上调有关。小鼠Y长臂编码许多不同的转录本,每个转录本都来自多个基因拷贝。在这些多拷贝基因中,最近描述的Sly被认为是与Y长臂缺失相关的精子发生缺陷的潜在基因。为了评估Sly的候选资格,在睾丸中从转录本和蛋白质水平检测了该基因的表达。Sly在次级精母细胞和圆形精子细胞的第一次减数分裂后转录,编码两个转录变体Sly_v1和Sly_v2(蛋白质称为SLY1和SLY2)。我们制备了一种针对SLY1的抗体,该抗体在圆形和早期伸长的精子细胞中检测到了该蛋白质,其主要位于细胞质中。酵母双杂交和免疫共沉淀研究表明,SLY1与顶体蛋白DKKL1、组蛋白乙酰转移酶KAT5(也称为TIP60)和微管相关蛋白APPBP2相互作用。这些数据共同表明,SLY1可能参与精子发生过程中的多个过程,包括基因表达的控制以及顶体的发育或功能。