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.

Genome-wide definition of promoter and enhancer usage during neural induction of human embryonic stem cells / Poletti, Valentina; Delli Carri, Alessia; Malagoli Tagliazucchi, Guidantonio; Faedo, Andrea; Petiti, Luca; Mazza, Emilia Maria Cristina; Peano, Clelia; De Bellis, Gianluca; Bicciato, Silvio; Miccio, Annarita; Cattaneo, Elena; Mavilio, Fulvio. - In: PLOS ONE. - ISSN 1932-6203. - 10:5(2015), pp. 1-24. [10.1371/journal.pone.0126590]

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

Poletti, Valentina;Malagoli Tagliazucchi, Guidantonio;MAZZA, Emilia Maria Cristina;De Bellis, Gianluca;BICCIATO, Silvio;MICCIO, ANNARITA;MAVILIO, Fulvio
2015

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.
10
5
1
24
Genome-wide definition of promoter and enhancer usage during neural induction of human embryonic stem cells / Poletti, Valentina; Delli Carri, Alessia; Malagoli Tagliazucchi, Guidantonio; Faedo, Andrea; Petiti, Luca; Mazza, Emilia Maria Cristina; Peano, Clelia; De Bellis, Gianluca; Bicciato, Silvio; Miccio, Annarita; Cattaneo, Elena; Mavilio, Fulvio. - In: PLOS ONE. - ISSN 1932-6203. - 10:5(2015), pp. 1-24. [10.1371/journal.pone.0126590]
Poletti, Valentina; Delli Carri, Alessia; Malagoli Tagliazucchi, Guidantonio; Faedo, Andrea; Petiti, Luca; Mazza, Emilia Maria Cristina; Peano, Clelia; De Bellis, Gianluca; Bicciato, Silvio; Miccio, Annarita; Cattaneo, Elena; Mavilio, Fulvio
File in questo prodotto:
File Dimensione Formato  
Poletti et al., PLoS One 2015.pdf

accesso aperto

Tipologia: Versione dell'editore (versione pubblicata)
Dimensione 6.62 MB
Formato Adobe PDF
6.62 MB Adobe PDF Visualizza/Apri
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

Licenza Creative Commons
I metadati presenti in IRIS UNIMORE sono rilasciati con licenza Creative Commons CC0 1.0 Universal, mentre i file delle pubblicazioni sono rilasciati con licenza Attribuzione 4.0 Internazionale (CC BY 4.0), salvo diversa indicazione.
In caso di violazione di copyright, contattare Supporto Iris

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11380/1074765
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 3
  • ???jsp.display-item.citation.isi??? 3
social impact