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XBP1s cutnrun


ABSTRACT: Epithelial mesenchymal plasticity (EMP) is a complex cellular reprogramming event that plays a major role in tissue homeostasis to infections and injury. Recently we elucidated a mechanism wherein the unfolded protein response (UPR) triggers EMP through the inositol-requiring protein 1 (IRE1α)–X-box-binding protein 1 (XBP1) axis, enhancing glucose shunting to protein N glycosylation producing ER stress. To better the genomic targets for the IRE1-XBP1 pathway that activate compensatory metabolic changes in EMP, we systematically identified the genomic XBP1 targets using Cleavage Under Targets and Release Using Nuclease (CUT&RUN) of a FLAG-epitope tagged XBP1 in RSV infection. CUT&RUN identified 7,086 enriched binding sites mapped to 4,827 genes; of these XBP1 binds to 2,119 sites within 1 kb of the transcription start sites. Interestingly, XBP1 binds to 322 superenhancers associated with RHO GTPase signaling that were associated with largely inert gene expression. By contrast, XBP1 binds to proximal promoters inducing coordinate mRNA expression of hexosamine biosynthetic enzymes encoding sequential steps in UDP-GlcNAc biosynthesis through AGCTCA motifs. We demonstrate that IRE1-XBP1 signaling is necessary and sufficient to activate core HBP enzymatic pathway by recruiting transcriptional elongation-competent phospho-Ser2 CTD modified RNA Pol II (pSer-PolII).

ORGANISM(S): Homo sapiens

PROVIDER: GSE214786 | GEO | 2023/01/02

REPOSITORIES: GEO

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