Functional assessment of heart-specific enhancers by integrating ChIP-seq data

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.

Automated summary

This study provides an integrative analysis pipeline for ChIP-seq data and identifies a comprehensive catalog of human heart-specific enhancers. Functional validation shows that 67% of the identified enhancers have reproducible activity in the heart.