Dynamic Transcriptional and Epigenetic Regulation of Human Epidermal Keratinocyte Differentiation.
Stem Cell Reports
; 6(4): 618-632, 2016 Apr 12.
Article
em En
| MEDLINE
| ID: mdl-27050947
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco
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Transcrição Gênica
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Queratinócitos
/
Diferenciação Celular
/
Epigênese Genética
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
/
Male
Idioma:
En
Revista:
Stem Cell Reports
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos