title: Large-scale discovery of enhancers from human heart tissue.
abstract: 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.
authors.affiliation: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors.forename: Dalit
authors.initials: D
authors.lastname: May
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Blow
authors.forename: Tommy
authors.initials: T
authors.lastname: Kaplan
authors.forename: David J
authors.initials: DJ
authors.lastname: McCulley
authors.forename: Brian C
authors.initials: BC
authors.lastname: Jensen
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Akiyama
authors.forename: Amy
authors.initials: A
authors.lastname: Holt
authors.forename: Ingrid
authors.initials: I
authors.lastname: Plajzer-Frick
authors.forename: Malak
authors.initials: M
authors.lastname: Shoukry
authors.forename: Crystal
authors.initials: C
authors.lastname: Wright
authors.forename: Veena
authors.initials: V
authors.lastname: Afzal
authors.forename: Paul C
authors.initials: PC
authors.lastname: Simpson
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rubin
authors.forename: Brian L
authors.initials: BL
authors.lastname: Black
authors.forename: James
authors.initials: J
authors.lastname: Bristow
authors.forename: Len A
authors.initials: LA
authors.lastname: Pennacchio
authors.forename: Axel
authors.initials: A
authors.lastname: Visel
mesh_terms: D000328:Adult; D000818:Animals; D002874:Chromosome Mapping; D004742:Enhancer Elements, Genetic; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology / Q000502:physiology*; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D050880:p300-CBP Transcription Factors
chemical_list: D050880:p300-CBP Transcription Factors