Architectural Proteins and Pluripotency Factors Cooperate to Orchestrate the Transcriptional Response of hESCs to Temperature Stress

Xiaowen Lyu, M. Jordan Rowley, Victor G. Corces

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Cells respond to temperature stress via up- and downregulation of hundreds of genes. This process is thought to be regulated by the heat shock factor HSF1, which controls the release of RNAPII from promoter-proximal pausing. Here, we analyze the events taking place in hESCs upstream of RNAPII release. We find that temperature stress results in the activation or decommissioning of thousands of enhancers. This process involves alterations in the occupancy of transcription factors HSF1, AP-1, NANOG, KLF4, and OCT4 accompanied by nucleosome remodeling by BRG1 and changes in H3K27ac. Furthermore, redistribution of RAD21 and CTCF results in the formation and disassembly of interactions mediated by these two proteins. These alterations tether and untether enhancers to their cognate promoters or refashion insulated neighborhoods, thus transforming the landscape of enhancer-promoter interactions. Details of the 3D interactome remodeling process support loop extrusion initiating at random sites as a mechanism for the establishment of CTCF/cohesin loops. Lyu et al. show that AP-1 and pluripotency factors play a critical role in the temperature stress response in hESCs. Recruitment of these factors to regulatory sequences is accompanied by changes in chromatin 3D organization mediated by CTCF and cohesin, which regulate the establishment of new enhancer-promoter interaction via a randomly initiated loop extrusion mechanism.

Original languageEnglish (US)
Pages (from-to)940-955.e7
JournalMolecular Cell
Volume71
Issue number6
DOIs
StatePublished - Sep 20 2018

Keywords

  • AP-1
  • CTCF
  • cohesin
  • enhancer
  • heat shock
  • loop extrusion
  • pluripotency
  • stem cell
  • transcription

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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