GSE105028
Architectural proteins and pluripotency factors cooperate to orchestrate the transcriptional response of hESCs to temperature stress
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. Overall design: Hi-C, HiChIP, ChIP-seq, ATAC-seq, eU-Seq