Heat shock transcription factor 1 localizes to sex chromatin during meiotic repression.
Heat shock transcription factor 1 localizes to sex chromatin during meiotic repression.
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DOI：
10.1074/jbc.m110.157552
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发表时间：
2010-11-05
期刊：
影响因子：
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通讯作者：
Henriksson E
中科院分区：
文献类型：
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作者：
Akerfelt M;Vihervaara A;Laiho A;Conter A;Christians ES;Sistonen L;Henriksson E
热休克因子1（HSF 1）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。Hsf 1和另一个HSF家族成员Hsf 2的破坏导致小鼠雄性不育和完全缺乏成熟精子，但HSF 1在精子发生中的具体作用仍不清楚。在这里，我们表明，HSF 1是瞬时表达的减数分裂精母细胞和单倍体圆形精子细胞在小鼠睾丸。Hsf 1 −/−雄性小鼠的曲细精管区域仅包含精原细胞，精子头部的形态异常增加。在寻找HSF 1靶基因时，我们在小鼠睾丸中鉴定了742个推定的启动子。其中，在减数分裂后细胞中表达的性染色体多拷贝基因被HSF 1占据。考虑到性染色质大多在减数分裂期间和之后被抑制，因此值得注意的是，HSF 1在减数分裂后抑制期间直接调节性连锁多拷贝基因的转录。此外，我们的研究结果表明，HSF 1定位于性体减数分裂前和完成减数分裂后的性染色体中心。据我们所知，HSF 1是第一个在减数分裂过程中被抑制的性染色质中发现的转录因子。
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.