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Prmt6 represses the pro-adipogenic Ppar-gamma-C/ebp-alpha transcription factor loop.
Gerstner, Mirjam; Heller, Vivien; Fechner, Johannes; Hermann, Benedikt; Wang, Lei; Lausen, Joern.
Afiliación
  • Gerstner M; Department of Eukaryotic Genetics, Institute of Biomedical Genetics, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
  • Heller V; Department of Eukaryotic Genetics, Institute of Biomedical Genetics, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
  • Fechner J; Department of Eukaryotic Genetics, Institute of Biomedical Genetics, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
  • Hermann B; Department of Eukaryotic Genetics, Institute of Biomedical Genetics, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
  • Wang L; Department of Eukaryotic Genetics, Institute of Biomedical Genetics, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany.
  • Lausen J; Department of Eukaryotic Genetics, Institute of Biomedical Genetics, University of Stuttgart, Allmandring 31, 70569, Stuttgart, Germany. joern.lausen@ibmg.uni-stuttgart.de.
Sci Rep ; 14(1): 6656, 2024 03 20.
Article en En | MEDLINE | ID: mdl-38509237
ABSTRACT
The feed-forward loop between the transcription factors Ppar-gamma and C/ebp-alpha is critical for lineage commitment during adipocytic differentiation. Ppar-gamma interacts with epigenetic cofactors to activate C/ebp-alpha and the downstream adipocytic gene expression program. Therefore, knowledge of the epigenetic cofactors associated with Ppar-gamma, is central to understanding adipocyte differentiation in normal differentiation and disease. We found that Prmt6 is present with Ppar-gamma on the Ppar-gamma and C/ebp-alpha promoter. It contributes to the repression of C/ebp-alpha expression, in part through its ability to induce H3R2me2a. During adipocyte differentiation, Prmt6 expression is reduced and the methyltransferase leaves the promoters. As a result, the expression of Ppar-gamma and C/ebp-alpha is upregulated and the adipocytic gene expression program is established. Inhibition of Prmt6 by a small molecule enhances adipogenesis, opening up the possibility of epigenetic manipulation of differentiation. Our data provide detailed information on the molecular mechanism controlling the Ppar-gamma-C/ebp-alpha feed-forward loop. Thus, they advance our understanding of adipogenesis in normal and aberrant adipogenesis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Adipogénesis Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Factores de Transcripción / Adipogénesis Límite: Animals Idioma: En Revista: Sci Rep Año: 2024 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Reino Unido