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PLZF targets developmental enhancers for activation during osteogenic differentiation of human mesenchymal stem cells.
Agrawal Singh, Shuchi; Lerdrup, Mads; Gomes, Ana-Luisa R; van de Werken, Harmen Jg; Vilstrup Johansen, Jens; Andersson, Robin; Sandelin, Albin; Helin, Kristian; Hansen, Klaus.
Afiliação
  • Agrawal Singh S; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Lerdrup M; Department of Hematology, Cambridge Institute for Medical Research and Welcome Trust/MRC Stem Cell Institute, University of Cambridge, Cambridge, United Kingdom.
  • Gomes AR; Centre for Epigenetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • van de Werken HJ; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Vilstrup Johansen J; Centre for Epigenetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Andersson R; Biotech Research and Innovation Centre (BRIC), Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Sandelin A; Centre for Epigenetics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Helin K; Department of Cell Biology, University Medical Center, Rotterdam, Netherlands.
  • Hansen K; Cancer Computational Biology Center, University Medical Center, Rotterdam, Netherlands.
Elife ; 82019 01 23.
Article em En | MEDLINE | ID: mdl-30672466
ABSTRACT
The PLZF transcription factor is essential for osteogenic differentiation of hMSCs; however, its regulation and molecular function during this process is not fully understood. Here, we revealed that the ZBTB16 locus encoding PLZF, is repressed by Polycomb (PcG) and H3K27me3 in naive hMSCs. At the pre-osteoblast stage of differentiation, the locus lost PcG binding and H3K27me3, gained JMJD3 recruitment, and H3K27ac resulting in high expression of PLZF. Subsequently, PLZF was recruited to osteogenic enhancers, influencing H3K27 acetylation and expression of nearby genes important for osteogenic function. Furthermore, we identified a latent enhancer within the ZBTB16/PLZF locus itself that became active, gained PLZF, p300 and Mediator binding and looped to the promoter of the nicotinamide N-methyltransferase (NNMT) gene. The increased expression of NNMT correlated with a decline in SAM levels, which is dependent on PLZF and is required for osteogenic differentiation.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteogênese / Diferenciação Celular / Elementos Facilitadores Genéticos / Desenvolvimento Embrionário / Células-Tronco Mesenquimais / Proteína com Dedos de Zinco da Leucemia Promielocítica Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Elife Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Dinamarca

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteogênese / Diferenciação Celular / Elementos Facilitadores Genéticos / Desenvolvimento Embrionário / Células-Tronco Mesenquimais / Proteína com Dedos de Zinco da Leucemia Promielocítica Tipo de estudo: Prognostic_studies Limite: Humans Idioma: En Revista: Elife Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Dinamarca