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

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.

SUBMITTER: Lyu X

PROVIDER: S-EPMC6214669 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Architectural proteins and pluripotency factors cooperate to orchestrate the transcriptional response of hESCs to temperature stress

Project description:Cells respond to temperature stress via up- and down-regulation of hundreds of genes. This process is regulated by the heat shock factor HSF1, which controls the release of RNAPII from promoter-proximal pausing. Here we analyze the events taking place upstream of transcription elongation in hESCs. 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, which is accompanied by changes in H3K27ac and H3K27me3, as well as nucleosome remodeling by BRG1. In addition, redistribution of RAD21 and CTCF results in the formation and disassembly of interactions mediated by these two proteins, either individually or in combination. These alterations either tether/untether enhancers to their cognate promoters or remodel insulated neighborhoods with the ultimate goal of transforming the landscape of enhancer-promoter interactions. This loop remodeling process supports unidirectional loop extrusion as a mechanism for the establishment of CTCF/cohesin loops.

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Architectural proteins and pluripotency factors cooperate to orchestrate the transcriptional response of hESCs to temperature stress

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