TY - JOUR
T1 - HACER
T2 - An atlas of human active enhancers to interpret regulatory variants
AU - Wang, Jing
AU - Dai, Xizhen
AU - Berry, Lynne D.
AU - Cogan, Joy D.
AU - Liu, Qi
AU - Shyr, Yu
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2019/1/8
Y1 - 2019/1/8
N2 - 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.
AB - 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.
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U2 - 10.1093/nar/gky864
DO - 10.1093/nar/gky864
M3 - Article
C2 - 30247654
AN - SCOPUS:85059797293
SN - 0305-1048
VL - 47
SP - D106-D112
JO - Nucleic acids research
JF - Nucleic acids research
IS - D1
ER -