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Systematic mapping of functional enhancer-promoter connections with CRISPR interference.
- Source :
-
Science (New York, N.Y.) [Science] 2016 Nov 11; Vol. 354 (6313), pp. 769-773. Date of Electronic Publication: 2016 Sep 29. - Publication Year :
- 2016
-
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.<br /> (Copyright © 2016, American Association for the Advancement of Science.)
- Subjects :
- CRISPR-Cas Systems
Cell Proliferation genetics
Disease genetics
Enhancer Elements, Genetic genetics
GATA1 Transcription Factor genetics
Gene Expression Regulation
Humans
K562 Cells
Promoter Regions, Genetic genetics
Proto-Oncogene Proteins c-myc genetics
Real-Time Polymerase Chain Reaction
Chromosome Mapping methods
Clustered Regularly Interspaced Short Palindromic Repeats
Enhancer Elements, Genetic physiology
High-Throughput Nucleotide Sequencing methods
Promoter Regions, Genetic physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 354
- Issue :
- 6313
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 27708057
- Full Text :
- https://doi.org/10.1126/science.aag2445