title: ChIP-Seq identification of weakly conserved heart enhancers.
abstract: Accurate control of tissue-specific gene expression plays a pivotal role in heart development, but few cardiac transcriptional enhancers have thus far been identified. Extreme noncoding-sequence conservation has successfully predicted enhancers that are active in many tissues but has failed to identify substantial numbers of heart-specific enhancers. Here, we used ChIP-Seq with the enhancer-associated protein p300 from mouse embryonic day 11.5 heart tissue to identify over 3,000 candidate heart enhancers genome wide. Compared to enhancers active in other tissues we studied at this time point, most candidate heart enhancers were less deeply conserved in vertebrate evolution. Nevertheless, transgenic mouse assays of 130 candidate regions revealed that most function reproducibly as enhancers active in the heart, irrespective of their degree of evolutionary constraint. These results provide evidence for a large population of poorly conserved heart enhancers and suggest that the evolutionary conservation of embryonic enhancers can vary depending on tissue type.
authors: Genomics Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.
authors: Matthew J
authors: MJ
authors: Blow
authors: David J
authors: DJ
authors: McCulley
authors: Zirong
authors: Z
authors: Li
authors: Tao
authors: T
authors: Zhang
authors: Jennifer A
authors: JA
authors: Akiyama
authors: Amy
authors: A
authors: Holt
authors: Ingrid
authors: I
authors: Plajzer-Frick
authors: Malak
authors: M
authors: Shoukry
authors: Crystal
authors: C
authors: Wright
authors: Feng
authors: F
authors: Chen
authors: Veena
authors: V
authors: Afzal
authors: James
authors: J
authors: Bristow
authors: Bing
authors: B
authors: Ren
authors: Brian L
authors: BL
authors: Black
authors: Edward M
authors: EM
authors: Rubin
authors: Axel
authors: A
authors: Visel
authors: Len A
authors: LA
authors: Pennacchio
mesh_terms: D000818:Animals; D001483:Base Sequence; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D017124:Conserved Sequence / Q000235:genetics; D004622:Embryo, Mammalian; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000196:embryology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism*; D009928:Organ Specificity / Q000235:genetics; D010802:Phylogeny; D017422:Sequence Analysis, DNA / Q000379:methods*; D014714:Vertebrates / Q000235:genetics / Q000378:metabolism