Erythropoietin Regulates Transcription and YY1 Dynamics in a Pre-established Chromatin Architecture.

Andrea A Perreault,Bryan J Venters,Jonathan D Brown

doi:10.1016/j.isci.2020.101583

Andrea A Perreault, Bryan J Venters + Show 1 more

Open Access

https://doi.org/10.1016/j.isci.2020.101583

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Abstract

SummaryThe 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.

Highlights

Transcription control is a primary mechanism for regulating gene expression in eukaryotes
The magnitude and temporal kinetics of changes in chromatin structure that arise during cell differentiation remain poorly understood
We leverage a murine model of erythropoiesis to study the relationship between chromatin conformation, the epigenome, and transcription in erythroid cells

Summary

Introduction

Transcription control is a primary mechanism for regulating gene expression in eukaryotes. Multiple mechanisms exist to regulate each step, thereby providing precise control over the magnitude and kinetics of transcription and global gene expression. Promoter proximal pausing is one such mechanism and is recognized as a general feature of transcription at many eukaryotic genes. Transcription factor (TF)-bound enhancers activate Pol II, acting as an additional mechanism in regulating transcription (Heintzman et al, 2009) and defining cell identity (Ernst et al, 2011; Zhu et al, 2013). Athough chromatin state maps are useful to assign enhancers to target genes based on distance from promoters, proximity analysis is overly simplistic with respect to the true gene regulatory environment (Mora et al, 2016; Yao et al, 2015; Rao et al, 2014)

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