Department of Biosciences, Åbo Akademi University, FI-20521 Turku, Finland.
J Biol Chem. 2010 Nov 5;285(45):34469-76. doi: 10.1074/jbc.M110.157552. Epub 2010 Aug 27.
Heat shock factor 1 (HSF1) is an important transcription factor in cellular stress responses, cancer, aging, and developmental processes including gametogenesis. Disruption of Hsf1, together with another HSF family member, Hsf2, causes male sterility and complete lack of mature sperm in mice, but the specific role of HSF1 in spermatogenesis has remained unclear. Here, we show that HSF1 is transiently expressed in meiotic spermatocytes and haploid round spermatids in mouse testis. The Hsf1(-/-) male mice displayed regions of seminiferous tubules containing only spermatogonia and increased morphological abnormalities in sperm heads. In search for HSF1 target genes, we identified 742 putative promoters in mouse testis. Among them, the sex chromosomal multicopy genes that are expressed in postmeiotic cells were occupied by HSF1. Given that the sex chromatin mostly is repressed during and after meiosis, it is remarkable that HSF1 directly regulates the transcription of sex-linked multicopy genes during postmeiotic repression. In addition, our results show that HSF1 localizes to the sex body prior to the meiotic divisions and to the sex chromocenter after completed meiosis. To the best of our knowledge, HSF1 is the first known transcription factor found at the repressed sex chromatin during meiosis.
热休克因子 1(HSF1)是细胞应激反应、癌症、衰老和发育过程(包括配子发生)中的重要转录因子。HSF1 和另一个 HSF 家族成员 Hsf2 的破坏会导致雄性不育和小鼠成熟精子完全缺乏,但 HSF1 在精子发生中的具体作用仍不清楚。在这里,我们表明 HSF1 在小鼠睾丸的减数分裂精母细胞和单倍体圆形精子中瞬时表达。Hsf1(-/-) 雄性小鼠显示出仅含有精原细胞的曲细精管区域,并增加了精子头部的形态异常。在寻找 HSF1 靶基因时,我们在小鼠睾丸中鉴定出了 742 个推定启动子。其中,在减数分裂后细胞中表达的性染色体多拷贝基因被 HSF1 占据。鉴于性染色质在减数分裂期间和之后大多被抑制,HSF1 直接在减数分裂后抑制期间调节性连锁多拷贝基因的转录是很显著的。此外,我们的结果表明,HSF1 在减数分裂之前定位于性体,在减数分裂完成后定位于性染色质中心。据我们所知,HSF1 是在减数分裂过程中在被抑制的性染色质上发现的第一个已知转录因子。