title: Dynamic Transcriptional and Epigenetic Regulation of Human Epidermal Keratinocyte Differentiation.
abstract: Human skin is maintained by the differentiation and maturation of interfollicular stem and progenitors cells. We used DeepCAGE, genome-wide profiling of histone modifications and retroviral integration analysis, to map transcripts, promoters, enhancers, and super-enhancers (SEs) in prospectively isolated keratinocytes and transit-amplifying progenitors, and retrospectively defined keratinocyte stem cells. We show that >95% of the active promoters are in common and differentially regulated in progenitors and differentiated keratinocytes, while approximately half of the enhancers and SEs are stage specific and account for most of the epigenetic changes occurring during differentiation. Transcription factor (TF) motif identification and correlation with TF binding site maps allowed the identification of TF circuitries acting on enhancers and SEs during differentiation. Overall, our study provides a broad, genome-wide description of chromatin dynamics and differential enhancer and promoter usage during epithelial differentiation, and describes a novel approach to identify active regulatory elements in rare stem cell populations.
authors.affiliation: Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Alessia
authors.initials: A
authors.lastname: Cavazza
authors.affiliation: Imagine Institute, 75015 Paris, France.
authors.forename: Annarita
authors.initials: A
authors.lastname: Miccio
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors.forename: Oriana
authors.initials: O
authors.lastname: Romano
authors.affiliation: Institute for Biomedical Technologies, National Research Council, 20132 Milan, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Petiti
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors.forename: Guidantonio
authors.initials: G
authors.lastname: Malagoli Tagliazucchi
authors.affiliation: Institute for Biomedical Technologies, National Research Council, 20132 Milan, Italy.
authors.forename: Clelia
authors.initials: C
authors.lastname: Peano
authors.affiliation: Institute for Biomedical Technologies, National Research Council, 20132 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Severgnini
authors.affiliation: Institute for Biomedical Technologies, National Research Council, 20132 Milan, Italy.
authors.forename: Ermanno
authors.initials: E
authors.lastname: Rizzi
authors.affiliation: Institute for Biomedical Technologies, National Research Council, 20132 Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: De Bellis
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Bicciato
authors.affiliation: Department of Life Sciences, University of Modena and Reggio Emilia, 41125 Modena, Italy; Genethon, 1bis rue de l'Internationale, 91002 Evry, France. Electronic address: fmavilio@genethon.fr.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Mavilio
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics*; D002478:Cells, Cultured; D004742:Enhancer Elements, Genetic / Q000235:genetics; D000078404:Epidermal Cells; D044127:Epigenesis, Genetic; D052816:Foreskin / Q000166:cytology; D020869:Gene Expression Profiling / Q000379:methods; D063990:Gene Ontology; D053263:Gene Regulatory Networks; D006657:Histones / Q000378:metabolism; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008957:Models, Genetic; D041681:NIH 3T3 Cells; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D006657:Histones; D014157:Transcription Factors