Perreault Andrea A, Brown Jonathan D, Venters Bryan J
Chemical and Physical Biology Program, Vanderbilt University, Nashville, TN 37232, USA.
Molecular Physiology and Biophysics, Vanderbilt University, Nashville, TN 37232, USA.
iScience. 2020 Sep 20;23(10):101583. doi: 10.1016/j.isci.2020.101583. eCollection 2020 Oct 23.
The three-dimensional architecture of the genome plays an essential role in establishing and maintaining cell identity. However, the magnitude and temporal kinetics of changes in chromatin structure that arise during cell differentiation remain poorly understood. Here, we leverage a murine model of erythropoiesis to study the relationship between chromatin conformation, the epigenome, and transcription in erythroid cells. We discover that acute transcriptional responses induced by erythropoietin (EPO), the hormone necessary for erythroid differentiation, occur within an invariant chromatin topology. Within this pre-established landscape, Yin Yang 1 (YY1) occupancy dynamically redistributes to sites in proximity of EPO-regulated genes. Using HiChIP, we identify chromatin contacts mediated by H3K27ac and YY1 that are enriched for enhancer-promoter interactions of EPO-responsive genes. Taken together, these data are consistent with an emerging model that rapid, signal-dependent transcription occurs in the context of a pre-established chromatin architecture.
基因组的三维结构在建立和维持细胞特性方面起着至关重要的作用。然而，细胞分化过程中染色质结构变化的幅度和时间动力学仍知之甚少。在这里，我们利用红细胞生成的小鼠模型来研究红系细胞中染色质构象、表观基因组和转录之间的关系。我们发现，促红细胞生成素（EPO）（红系分化所必需的激素）诱导的急性转录反应发生在不变的染色质拓扑结构内。在这个预先建立的格局中，阴阳1（YY1）的占据动态重新分布到EPO调控基因附近的位点。使用HiChIP，我们鉴定了由H3K27ac和YY1介导的染色质接触，这些接触富含EPO反应基因的增强子-启动子相互作用。综上所述，这些数据与一个新出现的模型一致，即快速的、信号依赖的转录发生在预先建立的染色质结构背景下。
