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Citation
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HERO ID
7424356
Reference Type
Journal Article
Title
Enhancer-promoter interactions are encoded by complex genomic signatures on looping chromatin
Author(s)
Whalen, S; Truty, RM; Pollard, KS; ,
Year
2016
Is Peer Reviewed?
1
Journal
Nature Genetics
ISSN:
1061-4036
EISSN:
1546-1718
Publisher
NATURE PUBLISHING GROUP
Location
NEW YORK
Page Numbers
488-496
Language
English
PMID
27064255
DOI
10.1038/ng.3539
Web of Science Id
WOS:000374834100006
URL
http://www.nature.com/articles/ng.3539
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Abstract
Discriminating the gene target of a distal regulatory element from other nearby transcribed genes is a challenging problem with the potential to illuminate the causal underpinnings of complex diseases. We present TargetFinder, a computational method that reconstructs regulatory landscapes from diverse features along the genome. The resulting models accurately predict individual enhancer-promoter interactions across multiple cell lines with a false discovery rate up to 15 times smaller than that obtained using the closest gene. By evaluating the genomic features driving this accuracy, we uncover interactions between structural proteins, transcription factors, epigenetic modifications, and transcription that together distinguish interacting from non-interacting enhancer-promoter pairs. Most of this signature is not proximal to the enhancers and promoters but instead decorates the looping DNA. We conclude that complex but consistent combinations of marks on the one-dimensional genome encode the three-dimensional structure of fine-scale regulatory interactions.
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