Analysis of estrogen-regulated enhancer RNAs identifies a functional motif required for enhancer assembly and gene expression.

ABSTRACT: To better understand the functions of non-coding enhancer RNAs (eRNAs), we annotated the estrogen-regulated eRNA transcriptome in estrogen receptor α (ERα)-positive breast cancer cells using PRO-cap and RNA sequencing. We then cloned a subset of the eRNAs identified, fused them to single guide RNAs, and targeted them to their ERα enhancers of origin using CRISPR/dCas9. Some of the eRNAs tested modulated the expression of cognate, but not heterologous, target genes after estrogen treatment by increasing ERα recruitment and stimulating p300-catalyzed H3K27 acetylation at the enhancer. We identified a ∼40 nucleotide functional eRNA regulatory motif (FERM) present in many eRNAs that was necessary and sufficient to modulate gene expression, but not the specificity of activation, after estrogen

SUBMITTER: Hou TY 

PROVIDER: S-EPMC9246336 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature