Multiplex Enhancer Interference Reveals Collaborative Control of Gene Regulation by Estrogen Receptor α-Bound Enhancers.

ABSTRACT: Multiple regulatory regions have the potential to regulate a single gene, yet how these elements combine to affect gene expression remains unclear. To uncover the combinatorial relationships between enhancers, we developed Enhancer-interference (Enhancer-i), a CRISPR interference-based approach that uses 2 different repressive domains, KRAB and SID, to prevent enhancer activation simultaneously at multiple regulatory regions. We applied Enhancer-i to promoter-distal estrogen receptor α binding sites (ERBS), which cluster around estradiol-responsive genes and therefore may collaborate to regulate gene expression. Targeting individual sites revealed predominant ERBS that are completely required for the transcriptional response, indicating a lack of redundancy. Simultaneous interference of di

SUBMITTER: Carleton JB 

PROVIDER: S-EPMC5679353 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature