Systematic mapping of functional enhancer-promoter connections with CRISPR interference.

Science
Authors
Abstract

Gene expression in mammals is regulated by noncoding elements that can affect physiology and disease, yet the functions and target genes of most noncoding elements remain unknown. We present a high-throughput approach that uses clustered regularly interspaced short palindromic repeats (CRISPR) interference (CRISPRi) to discover regulatory elements and identify their target genes. We assess >1 megabase of sequence in the vicinity of two essential transcription factors, MYC and GATA1, and identify nine distal enhancers that control gene expression and cellular proliferation. Quantitative features of chromatin state and chromosome conformation distinguish the seven enhancers that regulate MYC from other elements that do not, suggesting a strategy for predicting enhancer-promoter connectivity. This CRISPRi-based approach can be applied to dissect transcriptional networks and interpret the contributions of noncoding genetic variation to human disease.

Year of Publication
2016
Journal
Science
Volume
354
Issue
6313
Pages
769-773
Date Published
2016 Nov 11
ISSN
1095-9203
DOI
10.1126/science.aag2445
PubMed ID
27708057
Links
Grant list
P30 CA014051 / CA / NCI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
T32 GM087237 / GM / NIGMS NIH HHS / United States
Additional Materials