HACER: an atlas of human active enhancers to interpret regulatory variants

Abstract Recent studies have shown that disease-susceptibility variants frequently lie in cell-type-specific enhancer elements. To identify, interpret, and prioritize such risk variants, we must identify the enhancers active in disease-relevant cell types, their upstream transcription factor (TF) bi...

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Bibliographic Details
Published in:	Nucleic acids research Vol. 47; no. D1; pp. D106 - D112
Main Authors:	Wang, Jing, Dai, Xizhen, Berry, Lynne D, Cogan, Joy D, Liu, Qi, Shyr, Yu
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 08-01-2019
Subjects:	Computational Biology - methods Database Issue Databases, Genetic Enhancer Elements, Genetic Gene Expression Regulation Genetic Variation Genomics - methods Humans Web Browser
Online Access:	Get full text
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Summary:	Abstract Recent studies have shown that disease-susceptibility variants frequently lie in cell-type-specific enhancer elements. To identify, interpret, and prioritize such risk variants, we must identify the enhancers active in disease-relevant cell types, their upstream transcription factor (TF) binding, and their downstream target genes. To address this need, we built HACER (http://bioinfo.vanderbilt.edu/AE/HACER/), an atlas of Human ACtive Enhancers to interpret Regulatory variants. The HACER atlas catalogues and annotates in-vivo transcribed cell-type-specific enhancers, as well as placing enhancers within transcriptional regulatory networks by integrating ENCODE TF ChIP-Seq and predicted/validated chromatin interaction data. We demonstrate the utility of HACER in (i) offering a mechanistic hypothesis to explain the association of SNP rs614367 with ER-positive breast cancer risk, (ii) exploring tumor-specific enhancers in selective MYC dysregulation and (iii) prioritizing/annotating non-coding regulatory regions targeting CCND1. HACER provides a valuable resource for studies of GWAS, non-coding variants, and enhancer-mediated regulation.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0305-1048 1362-4962
DOI:	10.1093/nar/gky864