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Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells

机译:全球重组的人类胚胎干细胞沿袭承诺的顺式调节单位。

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摘要

Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understanding developmental transcriptional control. Here, we use Promoter Capture Hi-C to generate a high-resolution atlas of chromosomal interactions involving ~22,000 gene promoters in human pluripotent and lineage-committed cells, identifying putative target genes for known and predicted enhancer elements. We reveal extensive dynamics of cis-regulatory contacts upon lineage commitment, including the acquisition and loss of promoter interactions. This spatial rewiring occurs preferentially with predicted changes in the activity of cis-regulatory elements and is associated with changes in target gene expression. Our results provide a global and integrated view of promoter interactome dynamics during lineage commitment of human pluripotent cells.>DOI:
机译:远程顺式调控元件(例如增强子)通过与靶标启动子进行DNA循环相互作用来协调细胞特异性转录程序。理解谱系定型过程中启动子连接性与顺式调控元件活性之间的相互作用对理解发育转录控制至关重要。在这里,我们使用启动子捕获Hi-C来生成高分辨率的染色体相互作用图集,涉及人类多能和谱系定型细胞中的〜22,000个基因启动子,从而确定已知和预测的增强子元件的假定靶基因。我们揭示了沿袭承诺,包括获取和启动子相互作用的损失顺式调节接触的广泛动态。这种空间重排优先发生在顺式调控元件活性的预测变化中,并与靶基因表达的变化相关。我们的结果提供了人类多能细胞谱系定型过程中启动子相互作用组动力学的全局和综合视图。> DOI:

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