Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequences
Endonuclease-sensitive regions of human spermatozoal chromatin are highly enriched in promoter and CTCF binding sequences
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DOI：
10.1101/gr.094953.109
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发表时间：
2009-08-01
期刊：
影响因子：
7
通讯作者：
Miller, David
中科院分区：
文献类型：
--
作者：
Arpanahi, Ali;Brinkworth, Martin;Miller, David
在哺乳动物精子发生的单倍体阶段，核小体染色质最终被小而高碱性的鱼精蛋白重新包装，产生极其紧凑的环形染色质结构，这对精子的正常功能至关重要。然而，与几个物种一样，人类精子保留了一小部分包装在核小体中的染色质。由于精子中的核小体染色质在结构上比鱼精蛋白包装的染色质更开放，我们认为它可能更容易被外源应用的核酸内切酶接触。因此，我们利用这一前提来鉴定人类和小鼠精子中核酸内切酶敏感的 DNA 序列群体。我们的结果明确表明，与鱼精蛋白包装的耐核酸内切酶的精子染色质相比，核酸内切酶敏感性增加的区域与基因调控区域密切相关，包括许多启动子序列和 CCCTC 结合因子 (CTCF) 识别的序列。在小鼠和人的精子染色质中观察到类似的启动子差异包装。这些观察结果表明，表观遗传标记的存在可以区分雄性生殖细胞中的基因调控区域，并防止它们在精子发生过程中被鱼精蛋白重新包装。核酸内切酶敏感调节区控制下的基因本体论暗示了这种现象在随后的胚胎发育中的作用。
During the haploid phase of mammalian spermatogenesis, nucleosomal chromatin is ultimately repackaged by small, highly basic protamines to generate an extremely compact, toroidal chromatin architecture that is critical to normal spermatozoal function. In common with several species, however, the human spermatozoon retains a small proportion of its chromatin packaged in nucleosomes. As nucleosomal chromatin in spermatozoa is structurally more open than protamine-packaged chromatin, we considered it likely to be more accessible to exogenously applied endonucleases. Accordingly, we have used this premise to identify a population of endonuclease-sensitive DNA sequences in human and murine spermatozoa. Our results show unequivocally that, in contrast to the endonuclease-resistant sperm chromatin packaged by protamines, regions of increased endonuclease sensitivity are closely associated with gene regulatory regions, including many promoter sequences and sequences recognized by CCCTC-binding factor (CTCF). Similar differential packaging of promoters is observed in the spermatozoal chromatin of both mouse and man. These observations imply the existence of epigenetic marks that distinguish gene regulatory regions in male germ cells and prevent their repackaging by protamines during spermiogenesis. The ontology of genes under the control of endonuclease-sensitive regulatory regions implies a role for this phenomenon in subsequent embryonic development.