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Published on: June 21, 2016
Functional assessment of heart-specific enhancers by integrating ChIP-seq data
Feng Wang1,2, Yawen Zhang1,2, Fang Wu1,2
1Translational Medical Center for Development and Disease, Institute of Pediatrics, Key Laboratory of Birth Defects Prevention and Control, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, 201102, China.
Background:
Identification and functional annotations of regulatory sequences play a pivotal role in heart development and function.
Methods:
To generate a map of human heart-specific enhancers, we performed an integrative analysis of 148 chromatin immunoprecipitation coupled to massively parallel sequencing (ChIP-seq) samples with enhancer-associated epigenetic marks from the heart, liver, brain, and kidney. Functional validation of heart-specific enhancer activity was then performed using cultured cells.
Results:
A 144.6-Mb candidate heart-specific enhancer compendium was generated by integrating the analysis of 148 epigenomic data sets from human and mouse hearts and control tissues. To validate in vivo enhancer activity, we tested 12 of these sequences around 45 CHD-related genes in cultured cells and found that 8 (67%) have reproducible heart-specific enhancer activity. A functional analysis demonstrated that the identified human heart-specific enhancer wf1 regulates the FBN1 gene which is involved in heart disease.
Conclusions:
Our study provides an integrative analysis pipeline for ChIP-seq data and identified a comprehensive catalog of human heart-specific enhancers for clinical CHD-related studies.
Impact:
Establishing an efficient way to analyze regulatory regions in CHD is very important. A highly qualified heart-specific enhancer compendium was generated by integrating 148 online ChIP-seq samples. Sixty-seven percent of predicted regulatory sequences have reproducible heart-specific enhancer activity in vivo. Human heart-specific enhancer wf1 regulates the CHD-related FBN1 gene.
