Enhancers Regulate 3' End Processing Activity to Control Expression of Alternative 3'UTR Isoforms

Overview

Journal Nat Commun

Specialty Biology

Date 2022 May 17

PMID 35581194

Authors

Buki Kwon

Mervin M Fansler

Neil D Patel

Jihye Lee

Weirui Ma

Christine Mayr

Affiliations

Soon will be listed here.

Abstract

Multi-UTR genes are widely transcribed and express their alternative 3'UTR isoforms in a cell type-specific manner. As transcriptional enhancers regulate mRNA expression, we investigated if they also regulate 3'UTR isoform expression. Endogenous enhancer deletion of the multi-UTR gene PTEN did not impair transcript production but prevented 3'UTR isoform switching which was recapitulated by silencing of an enhancer-bound transcription factor. In reporter assays, enhancers increase transcript production when paired with single-UTR gene promoters. However, when combined with multi-UTR gene promoters, they change 3'UTR isoform expression by increasing 3' end processing activity of polyadenylation sites. Processing activity of polyadenylation sites is affected by transcription factors, including NF-κB and MYC, transcription elongation factors, chromatin remodelers, and histone acetyltransferases. As endogenous cell type-specific enhancers are associated with genes that increase their short 3'UTRs in a cell type-specific manner, our data suggest that transcriptional enhancers integrate cellular signals to regulate cell type-and condition-specific 3'UTR isoform expression.

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