title: The Wnt-target gene Dlk-1 is regulated by the Prmt5-associated factor Copr5 during adipogenic conversion.
abstract: Protein arginine methyl transferase 5 (Prmt5) regulates various differentiation processes, including adipogenesis. Here, we investigated adipogenic conversion in cells and mice in which Copr5, a Prmt5- and histone-binding protein, was genetically invalidated. Compared to control littermates, the retroperitoneal white adipose tissue (WAT) of Copr5 KO mice was slightly but significantly reduced between 8 and 16 week/old and contained fewer and larger adipocytes. Moreover, the adipogenic conversion of Copr5 KO embryoid bodies (EB) and of primary embryo fibroblasts (Mefs) was markedly delayed. Differential transcriptomic analysis identified Copr5 as a negative regulator of the Dlk-1 gene, a Wnt target gene involved in the control of adipocyte progenitors cell fate. Dlk-1 expression was upregulated in Copr5 KO Mefs and the Vascular Stromal Fraction (VSF) of Copr5 KO WAT. Chromatin immunoprecipitation (ChIP) show that the ablation of Copr5 has impaired both the recruitment of Prmt5 and β-catenin at the Dlk-1 promoter. Overall, our data suggest that Copr5 is involved in the transcriptional control exerted by the Wnt pathway on early steps of adipogenesis.
authors: Equipe labellisée Ligue Contre le Cancer, Institut de Génétique Moléculaire de Montpellier, CNRS, UMR5535, 34293 Montpellier, France Université Montpellier I and II, 34000 Montpellier, France.
authors: Conception
authors: C
authors: Paul
authors: Equipe labellisée Ligue Contre le Cancer, Institut de Génétique Moléculaire de Montpellier, CNRS, UMR5535, 34293 Montpellier, France Université Montpellier I and II, 34000 Montpellier, France Institut de Recherche en Cancérologie de Montpellier, Inserm, U1194, 34298 Montpellier, France eric.fabbrizio@igmm.cnrs.fr claude.sardet@igmm.cnrs.fr.
authors: Claude
authors: C
authors: Sardet
authors: Equipe labellisée Ligue Contre le Cancer, Institut de Génétique Moléculaire de Montpellier, CNRS, UMR5535, 34293 Montpellier, France Université Montpellier I and II, 34000 Montpellier, France Institut de Recherche en Cancérologie de Montpellier, Inserm, U1194, 34298 Montpellier, France eric.fabbrizio@igmm.cnrs.fr claude.sardet@igmm.cnrs.fr.
authors: Eric
authors: E
authors: Fabbrizio
keywords: Adipocyte; Copr5; Differentiation; Dlk-1; Prmt5; β-catenin