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 upregulated 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.

Genome-wide definition of promoter and enhancer usage during neural induction of human embryonic stem cells / V. Poletti, A.D. Carri, G.M. Tagliazucchi, A. Faedo, L. Petiti, E.M.C. Mazza, C. Peano, G. De Bellis, S. Bicciato, A. Miccio, E. Cattaneo, F. Mavilio. - In: PLOS ONE. - ISSN 1932-6203. - 10:5(2015 May 15), pp. 0126590.1-0126590.24. [10.1371/journal.pone.0126590]

Genome-wide definition of promoter and enhancer usage during neural induction of human embryonic stem cells

A.D. Carri;A. Faedo;L. Petiti;E.M.C. Mazza;E. Cattaneo;
2015-05-15

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 upregulated 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.
Cell Differentiation; Cell Line; Chromosome Mapping; Enhancer Elements, Genetic; Epigenesis, Genetic; Genome, Human; Genome-Wide Association Study; Histones; Human Embryonic Stem Cells; Humans; Neurons; Pluripotent Stem Cells; Promoter Regions, Genetic; RNA, Untranslated; Transcription Initiation Site; Transcription, Genetic; Up-Regulation; Biochemistry, Genetics and Molecular Biology (all); Agricultural and Biological Sciences (all)
Settore BIO/14 - Farmacologia
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2434/630793
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