基因组范围的 R 环景观在细胞分化和重编程过程中。

Genome-wide R-loop Landscapes during Cell Differentiation and Reprogramming.

机构信息

State Key Laboratory of Membrane Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.

State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing 100049, China.

出版信息

Cell Rep. 2020 Jul 7;32(1):107870. doi: 10.1016/j.celrep.2020.107870.

DOI:10.1016/j.celrep.2020.107870

PMID:32640235

Abstract

DNA

RNA hybrids play key roles in both physiological and disease states by regulating chromatin and genome organization. Their homeostasis during cell differentiation and cell plasticity remains elusive. Using an isogenic human stem cell platform, we systematically characterize R-loops, DNA methylation, histone modifications, and chromatin accessibility in pluripotent cells and their lineage-differentiated derivatives. We confirm that a portion of R-loops formed co-transcriptionally at pluripotency genes in pluripotent stem cells and at lineage-controlling genes in differentiated lineages. Notably, a subset of R-loops maintained after differentiation are associated with repressive chromatin marks on silent pluripotency genes and undesired lineage genes. Moreover, in reprogrammed pluripotent cells, cell-of-origin-specific R-loops are initially present but are resolved with serial passaging. Our analysis suggests a multifaceted role of R-loops in cell fate determination that may serve as an additional layer of modulation on cell fate memory and cell plasticity.

摘要

DNA

RNA 杂交在调节染色质和基因组组织方面，在生理和疾病状态中发挥关键作用。它们在细胞分化和细胞可塑性过程中的动态平衡仍然难以捉摸。我们使用同源人干细胞平台，系统地描述了多能细胞及其谱系分化衍生物中的 R 环、DNA 甲基化、组蛋白修饰和染色质可及性。我们证实，一部分 R 环在多能干细胞中的多能性基因和分化谱系中的谱系控制基因中在转录过程中形成。值得注意的是，分化后保留的一部分 R 环与沉默的多能性基因和不需要的谱系基因上的抑制性染色质标记有关。此外，在重编程的多能细胞中，细胞起源特异性 R 环最初存在，但随着连续传代而被解决。我们的分析表明，R 环在细胞命运决定中具有多方面的作用，它可能作为细胞命运记忆和细胞可塑性的额外调节层。