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Large-scale discovery of enhancers from human heart tissue
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Large-scale discovery of enhancers from human heart tissue
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Journal Article
Large-scale discovery of enhancers from human heart tissue
2012
Overview
Len Pennacchio, Axel Visel and colleagues use an epigenomic approach to identify a large number of candidate enhancers from human heart tissue. This work will facilitate further studies into the role of enhancers in human cardiac development and disease.
Development and function of the human heart depend on the dynamic control of tissue-specific gene expression by distant-acting transcriptional enhancers. To generate an accurate genome-wide map of human heart enhancers, we used an epigenomic enhancer discovery approach and identified ∼6,200 candidate enhancer sequences directly from fetal and adult human heart tissue. Consistent with their predicted function, these elements were markedly enriched near genes implicated in heart development, function and disease. To further validate their
in vivo
enhancer activity, we tested 65 of these human sequences in a transgenic mouse enhancer assay and observed that 43 (66%) drove reproducible reporter gene expression in the heart. These results support the discovery of a genome-wide set of noncoding sequences highly enriched in human heart enhancers that is likely to facilitate downstream studies of the role of enhancers in development and pathological conditions of the heart.
Publisher
Nature Publishing Group US,Nature Publishing Group
Subject
/ Adult
/ Animal Genetics and Genomics
/ Animals
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ Fundamental and applied biological sciences. Psychology
/ Gene Expression Regulation, Developmental
/ Genetics
/ Genetics of eukaryotes. Biological and molecular evolution
/ Genomes
/ Genomics
/ Humans
/ letter
/ Mice
/ p300-CBP Transcription Factors
/ Proteins
/ Single nucleotide polymorphisms
/ Studies
