Analysis of chromatin accessibility in decidualizing human endometrial stromal cells.
Analysis of chromatin accessibility in decidualizing human endometrial stromal cells.
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DOI：
10.1096/fj.201701098r
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发表时间：
2018-05
期刊：
影响因子：
--
通讯作者：
Ott S
中科院分区：
文献类型：
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作者：
Vrljicak P;Lucas ES;Lansdowne L;Lucciola R;Muter J;Dyer NP;Brosens JJ;Ott S
子宫内膜响应孕酮信号的自发蜕膜化仅限于哺乳动物，包括人类和其他高等灵长类动物。在此过程中，子宫内膜基质细胞（EnSC）分化为控制胚胎着床的特化蜕膜细胞。我们对未分化和蜕膜化的人EnSC进行了转座酶可及染色质测序（ATAC-seq）测定，以绘制潜在的染色质变化。共185，084个开放的DNA位点在EnSC中准确定位。蜕膜化后染色质可及性的改变与差异基因表达密切相关。对1533个开放和关闭染色质区域的分析揭示了已知蜕膜转录因子（TF）的DNA结合基序的过度表达，并确定了推定的新调节因子。ATAC-seq足迹分析提供了TF在特定基序处结合的证据。其中最大的足迹涉及最丰富的基序碱性亮氨酸拉链作为一个三重基序，也包括雌激素受体和Pax结构域结合位点的一部分。无一例外，三重基序位于Alu元件，这表明这种灵长类动物特异性转座因子（TE）在蜕膜基因的进化中的作用。虽然其他TE在未分化的EnSC的开放染色质中通常代表不足，但有几类有助于支持蜕膜基因表达的调控DNA景观。Vrljicak，P.，Lucas，E.美国，Lansdowne，L.卢乔拉河Muter，J.，Dyer，N. P.，Brosens，J. J.，奥特，S。人子宫内膜间质细胞蜕膜化过程中染色质可及性分析。
Spontaneous decidualization of the endometrium in response to progesterone signaling is confined to menstruating species, including humans and other higher primates. During this process, endometrial stromal cells (EnSCs) differentiate into specialized decidual cells that control embryo implantation. We subjected undifferentiated and decidualizing human EnSCs to an assay for transposase accessible chromatin with sequencing (ATAC-seq) to map the underlying chromatin changes. A total of 185,084 open DNA loci were mapped accurately in EnSCs. Altered chromatin accessibility upon decidualization was strongly associated with differential gene expression. Analysis of 1533 opening and closing chromatin regions revealed over-representation of DNA binding motifs for known decidual transcription factors (TFs) and identified putative new regulators. ATAC-seq footprint analysis provided evidence of TF binding at specific motifs. One of the largest footprints involved the most enriched motif—basic leucine zipper—as part of a triple motif that also comprised the estrogen receptor and Pax domain binding sites. Without exception, triple motifs were located within Alu elements, which suggests a role for this primate-specific transposable element (TE) in the evolution of decidual genes. Although other TEs were generally under-represented in open chromatin of undifferentiated EnSCs, several classes contributed to the regulatory DNA landscape that underpins decidual gene expression.—Vrljicak, P., Lucas, E. S., Lansdowne, L., Lucciola, R., Muter, J., Dyer, N. P., Brosens, J. J., Ott, S. Analysis of chromatin accessibility in decidualizing human endometrial stromal cells.