Promoter ChIP-chip analysis in mouse testis reveals Y chromosome occupancy by HSF2
Promoter ChIP-chip analysis in mouse testis reveals Y chromosome occupancy by HSF2
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DOI：
10.1073/pnas.0800620105
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发表时间：
2008-08-12
影响因子：
11.1
通讯作者：
Sistonen, Lea
中科院分区：
文献类型：
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作者：
Akerfelt, Malin;Henriksson, Eva;Sistonen, Lea
哺乳动物的Y染色体是精子发生所必需的，其特征在于精子细胞分化和染色质浓缩以获得正确的精子形状。小鼠Y染色体长臂（MSYq）的雄性特异性区域的缺失，携带了几个基因的多个拷贝，导致精子头部缺陷和生育能力受损。利用小鼠睾丸启动子芯片（ChIP芯片）上的染色质免疫沉淀，我们发现了一个惊人的热休克因子2（HSF 2），参与精子发生的转录因子在体内MSYq占用。还发现HSF 2调节MSYq驻留基因的转录，其转录调节是未知的。重要的是，Hsf 2的破坏引起与MSYq的2/3缺失相似的表型，即，改变多拷贝基因的表达和增加轻度精子头部异常。因此，检测到异常水平的染色质包装蛋白和更频繁的DNA片段化，这意味着HSF 2是精子中正确染色质组织所必需的。我们的研究结果定义了HSF 2在调节MSYq常驻基因和精子质量中的生理作用。
The mammalian Y chromosome is essential for spermatogenesis, which is characterized by sperm cell differentiation and chromatin condensation for acquisition of correct shape of the sperm. Deletions of the male-specific region of the mouse Y chromosome long arm (MSYq), harboring multiple copies of a few genes, lead to sperm head defects and impaired fertility. Using chromatin immunoprecipitation on promoter microarray (ChIP-chip) on mouse testis, we found a striking in vivo MSYq occupancy by heat shock factor 2 (HSF2), a transcription factor involved in spermatogenesis. HSF2 was also found to regulate the transcription of MSYq resident genes, whose transcriptional regulation has been unknown. Importantly, disruption of Hsf2 caused a similar phenotype as the 2/3 deletion of MSYq, i.e., altered expression of the multicopy genes and increased mild sperm head abnormalities. Consequently, aberrant levels of chromatin packing proteins and more frequent DNA fragmentation were detected, implying that HSF2 is required for correct chromatin organization in the sperm. Our findings define a physiological role for HSF2 in the regulation of MSYq resident genes and the quality of sperm.