title: ChIP-seq accurately predicts tissue-specific activity of enhancers.
abstract: A major yet unresolved quest in decoding the human genome is the identification of the regulatory sequences that control the spatial and temporal expression of genes. Distant-acting transcriptional enhancers are particularly challenging to uncover because they are scattered among the vast non-coding portion of the genome. Evolutionary sequence constraint can facilitate the discovery of enhancers, but fails to predict when and where they are active in vivo. Here we present the results of chromatin immunoprecipitation with the enhancer-associated protein p300 followed by massively parallel sequencing, and map several thousand in vivo binding sites of p300 in mouse embryonic forebrain, midbrain and limb tissue. We tested 86 of these sequences in a transgenic mouse assay, which in nearly all cases demonstrated reproducible enhancer activity in the tissues that were predicted by p300 binding. Our results indicate that in vivo mapping of p300 binding is a highly accurate means for identifying enhancers and their associated activities, and suggest that such data sets will be useful to study the role of tissue-specific enhancers in human biology and disease on a genome-wide scale.
authors.affiliation: Genomics Division, MS 84-171, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Axel
authors.initials: A
authors.lastname: Visel
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Blow
authors.forename: Zirong
authors.initials: Z
authors.lastname: Li
authors.forename: Tao
authors.initials: T
authors.lastname: Zhang
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: Feng
authors.initials: F
authors.lastname: Chen
authors.forename: Veena
authors.initials: V
authors.lastname: Afzal
authors.forename: Bing
authors.initials: B
authors.lastname: Ren
authors.forename: Edward M
authors.initials: EM
authors.lastname: Rubin
authors.forename: Len A
authors.initials: LA
authors.lastname: Pennacchio
mesh_terms: D000818:Animals; D047369:Chromatin Immunoprecipitation / Q000379:methods*; D002874:Chromosome Mapping / Q000379:methods*; D017124:Conserved Sequence; D004622:Embryo, Mammalian / Q000196:embryology; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D008636:Mesencephalon / Q000196:embryology*; D051379:Mice; D016548:Prosencephalon / Q000196:embryology*; D050880:p300-CBP Transcription Factors / Q000378:metabolism*; D000099224:p300-CBP-Associated Factor
chemical_list: D050880:p300-CBP Transcription Factors; D000099224:p300-CBP-Associated Factor