Your browser doesn't support javascript.
loading
14-3-3ζ regulates adipogenesis by modulating chromatin accessibility during the early stages of adipocyte differentiation.
Rial, S A; You, Z; Vivoli, A; Sean, D; Al-Khoury, Amal; Lavoie, G; Civelek, M; Martinez-Sanchez, A; Durcan, T M; Lim, G E.
Afiliación
  • Rial SA; Department of Medicine, Université de Montréal, Montreal, QC, Canada.
  • You Z; Cardiometabolic Axis, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
  • Vivoli A; The Neuro's Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC, H3A 2B4, Canada.
  • Sean D; Department of Medicine, Université de Montréal, Montreal, QC, Canada.
  • Al-Khoury A; Cardiometabolic Axis, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
  • Lavoie G; Department of Medicine, Université de Montréal, Montreal, QC, Canada.
  • Civelek M; Cardiometabolic Axis, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
  • Martinez-Sanchez A; Department of Medicine, Université de Montréal, Montreal, QC, Canada.
  • Roux Pp; Cardiometabolic Axis, Centre de Recherche du Centre Hospitalier de l'Université de Montréal (CRCHUM), Montreal, QC, Canada.
  • Durcan TM; Institute for Research in Immunology and Cancer (IRIC), Université de Montréal, Montréal, Québec, Canada.
  • Lim GE; Department of Pathology and Cell Biology, Faculty of Medicine, Université de Montréal, Montréal, Québec, Canada.
bioRxiv ; 2024 Mar 19.
Article en En | MEDLINE | ID: mdl-38562727
ABSTRACT
We previously established the scaffold protein 14-3-3ζ as a critical regulator of adipogenesis and adiposity, but the temporal specificity of its action during adipocyte differentiation remains unclear. To decipher if 14-3-3ζ exerts its regulatory functions on mature adipocytes or on adipose precursor cells (APCs), we generated Adipoq14-3-3ζKO and Pdgfra14-3-3ζKO mouse models. Our findings revealed a pivotal role for 14-3-3ζ in APC differentiation in a sex-dependent manner, whereby male and female Pdgfra14-3-3ζKO mice display impaired or potentiated weight gain, respectively, as well as fat mass. To better understand how 14-3-3ζ regulates the adipogenic transcriptional program in APCs, CRISPR-Cas9 was used to generate TAP-tagged 14-3-3ζ-expressing 3T3-L1 preadipocytes. Using these cells, we examined if the 14-3-3ζ nuclear interactome is enriched with adipogenic regulators during differentiation. Regulators of chromatin remodeling, such as DNMT1 and HDAC1, were enriched in the nuclear interactome of 14-3-3ζ, and their activities were impacted upon 14-3-3ζ depletion. The interactions between 14-3-3ζ and chromatin-modifying enzymes suggested that 14-3-3ζ may control chromatin remodeling during adipogenesis, and this was confirmed by ATAC-seq, which revealed that 14-3-3ζ depletion impacted the accessibility of up to 1,244 chromatin regions corresponding in part to adipogenic genes, promoters, and enhancers during the initial stages of adipogenesis. Moreover, 14-3-3ζ-dependent chromatin accessibility was found to directly correlate with the expression of key adipogenic genes. Altogether, our study establishes 14-3-3ζ as a crucial epigenetic regulator of adipogenesis and highlights the usefulness of deciphering the nuclear 14-3-3ζ interactome to identify novel pro-adipogenic factors and pathways.
Palabras clave
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: BioRxiv Año: 2024 Tipo del documento: Article País de afiliación: Canadá Pais de publicación: Estados Unidos