title: Genome-Wide Definition of Promoter and Enhancer Usage during Neural Induction of Human Embryonic Stem Cells.
abstract: Genome-wide mapping of transcriptional regulatory elements is an essential tool for understanding the molecular events orchestrating self-renewal, commitment and differentiation of stem cells. We combined high-throughput identification of transcription start sites with genome-wide profiling of histones modifications to map active promoters and enhancers in embryonic stem cells (ESCs) induced to neuroepithelial-like stem cells (NESCs). Our analysis showed that most promoters are active in both cell types while approximately half of the enhancers are cell-specific and account for most of the epigenetic changes occurring during neural induction, and most likely for the modulation of the promoters to generate cell-specific gene expression programs. Interestingly, the majority of the promoters activated or up-regulated during neural induction have a "bivalent" histone modification signature in ESCs, suggesting that developmentally-regulated promoters are already poised for transcription in ESCs, which are apparently pre-committed to neuroectodermal differentiation. Overall, our study provides a collection of differentially used enhancers, promoters, transcription starts sites, protein-coding and non-coding RNAs in human ESCs and ESC-derived NESCs, and a broad, genome-wide description of promoter and enhancer usage and of gene expression programs characterizing the transition from a pluripotent to a neural-restricted cell fate.
authors.affiliation: Division of Genetics and Cell Biology, Scientific Institute H. San Raffaele, Milan, Italy; Genethon, Evry, France.
authors.forename: Valentina
authors.initials: V
authors.lastname: Poletti
authors.affiliation: Department of Biosciences, University of Milano, Milan, Italy.
authors.forename: Alessia
authors.initials: A
authors.lastname: Delli Carri
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Guidantonio
authors.initials: G
authors.lastname: Malagoli Tagliazucchi
authors.affiliation: Department of Biosciences, University of Milano, Milan, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Faedo
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Petiti
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Emilia Maria Cristina
authors.initials: EM
authors.lastname: Mazza
authors.affiliation: Institute of Biomedical Technologies, National Research Council, Milan, Italy.
authors.forename: Clelia
authors.initials: C
authors.lastname: Peano
authors.affiliation: Institute of Biomedical Technologies, National Research Council, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: De Bellis
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy; Imagine Institute, Paris, France.
authors.forename: Annarita
authors.initials: A
authors.lastname: Miccio
authors.affiliation: Department of Biosciences, University of Milano, Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Cattaneo
authors.affiliation: Genethon, Evry, France; Department of Life Sciences, University of Modena and Reggio Emilia, Modena, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Mavilio
mesh_terms: D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D002874:Chromosome Mapping / Q000379:methods; D004742:Enhancer Elements, Genetic / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics; D015894:Genome, Human / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D006657:Histones / Q000235:genetics; D000066449:Human Embryonic Stem Cells / Q000166:cytology*; D006801:Humans; D009474:Neurons / Q000166:cytology; D039904:Pluripotent Stem Cells / Q000166:cytology; D011401:Promoter Regions, Genetic / Q000502:physiology*; D022661:RNA, Untranslated / Q000235:genetics; D024363:Transcription Initiation Site / Q000502:physiology; D014158:Transcription, Genetic / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics
chemical_list: D006657:Histones; D022661:RNA, Untranslated