Gonadal supporting cells acquire sex-specific chromatin landscapes during mammalian sex determination
Gonadal supporting cells acquire sex-specific chromatin landscapes during mammalian sex determination
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DOI：
10.1016/j.ydbio.2018.12.023
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发表时间：
2019-02-15
影响因子：
2.7
通讯作者：
Maatouk, Danielle M.
中科院分区：
文献类型：
--
作者：
Garcia-Moreno, S. Alexandra;Futtner, Christopher R.;Maatouk, Danielle M.
顺式调控元件在发育过程中对基因的精确时空调控至关重要。然而，由于全基因组表观遗传分析需要大量细胞，因此鉴定体内驱动细胞分化的功能调控位点变得复杂。在这里，我们通过在小鼠性别决定前后纯化的XX和XY性腺支持细胞中对H3K27ac进行ATAC-seq和ChIP-seq，确定了性别决定过程中可能的调节元件。我们发现，XX和XY支持细胞以相似的染色质景观启动性别决定，并在决定雄性或雌性命运时获得性别特异性调节元件。为了验证我们的方法，我们在促卵巢基因Bmp2的下游发现了一个功能性性腺特异性增强子。这项工作增加了我们对哺乳动物性别决定的复杂调控网络的理解，并为识别可能包含导致性发育障碍的突变的非编码调控元件提供了强大的资源。
Cis-regulatory elements are critical for the precise spatiotemporal regulation of genes during development. However, identifying functional regulatory sites that drive cell differentiation in vivo has been complicated by the high numbers of cells required for whole-genome epigenetic assays. Here, we identified putative regulatory elements during sex determination by performing ATAC-seq and ChIP-seq for H3K27ac in purified XX and XY gonadal supporting cells before and after sex determination in mice. We show that XX and XY supporting cells initiate sex determination with similar chromatin landscapes and acquire sex-specific regulatory elements as they commit to the male or female fate. To validate our approach, we identified a functional gonad-specific enhancer downstream of Bmp2, an ovary-promoting gene. This work increases our understanding of the complex regulatory network underlying mammalian sex determination and provides a powerful resource for identifying non-coding regulatory elements that could harbor mutations that lead to Disorders of Sexual Development.