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.
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.
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Human skin is maintained by the differentiation and maturation of interfollicular stem and progenitors cells. Hematopoietic stem cells, epigenetics, differentiationÄynamic Transcriptional and Epigenetic Regulation of Human Epidermal Keratinocyte DifferentiationĬavazza, Alessia, Miccio, Annarita, Romano, Oriana, Petiti, Luca, Tagliazucchi, Guidantonio Malagoli, Peano, Clelia, Severgnini, Marco, Rizzi, Ermanno, De Bellis, Gianluca, Bicciato, Silvio, Mavilio, Fulvio PETITI LUCA, DE BELLIS GIANLUCA, PEANO CLELIA, SEVERGNINI MARCO Scientific reports (Nature Publishing Group) 6 (2016). Overall, this study provides an overview of transcriptional and epigenetic changes associated to HSPC lineage commitment, and a novel signature for regulatory elements involved in cell identity. Expression analyses, together with an enhancer functional assay, indicate that MLV integration can be used to identify bona fide developmentally regulated enhancers. MLV-targeted genomic regions co-mapped with cell-specific active enhancers and super-enhancers. A significant fraction of CAGE promoters differentially expressed upon commitment were novel, harbored a chromatin enhancer signature, and may identify promoters and transcribed enhancers driving cell commitment. Most promoters and transcripts were shared by HSPC and committed progenitors, while enhancers and super-enhancers consistently changed upon differentiation, indicating that lineage commitment is essentially regulated by enhancer elements. Here, we define the transcriptional and epigenetic profile of human HSPC and early myeloid and erythroid progenitors by a combination of Cap Analysis of Gene Expression (CAGE), ChIP-seq and Moloney leukemia virus (MLV) integration site mapping.
Hematopoietic stem/progenitor cells (HSPC) give rise to the different blood cell types however, the molecular basis of human hematopoietic lineage commitment is poorly characterized. Genome-wide approaches allow investigating the molecular circuitry wiring the genetic and epigenetic programs of human somatic stem cells. Romano, Oriana, Peano, Clelia, Tagliazucchi, Guidantonio Malagoli, Petiti, Luca, Poletti, Valentina, Cocchiarella, Fabienne, Rizzi, Ermanno, Severgnini, Marco, Cavazza, Alessia, Rossi, Claudia, Pagliaro, Pasqualepaolo, Ambrosi, Alessandro, Ferrari, Giuliana, Bicciato, Silvio, De Bellis, Gianluca, Mavilio, Fulvio, Miccio, Annarita Transcriptional, epigenetic and retroviral signatures identify regulatory regions involved in hematopoietic lineage commitment