The LXCXE Retinoblastoma Protein-Binding Motif of FOG-2 Regulates Adipogenesis

Olivier Goupille; Tipparat Penglong; Zahra Kadri; Marine Granger-Locatelli; Raphaël Denis; Serge Luquet; Cécile Badoual; Suthat Fucharoen; Leila Maouche-Chrétien; Philippe Leboulch; Stany Chrétien

doi:10.1016/j.celrep.2017.11.098

The LXCXE Retinoblastoma Protein-Binding Motif of FOG-2 Regulates Adipogenesis

Cell Rep. 2017 Dec 19;21(12):3524-3535. doi: 10.1016/j.celrep.2017.11.098.

Affiliations

¹ Service des Thérapies Innovantes, Institute Jacob, CEA 92265 Fontenay-aux-Roses and University Paris Saclay UMR-E007, 91405 Orsay Cedex, France.
² Service des Thérapies Innovantes, Institute Jacob, CEA 92265 Fontenay-aux-Roses and University Paris Saclay UMR-E007, 91405 Orsay Cedex, France; Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, 73170 Nakhon Pathom, Thailand.
³ Unité de Biologie Fonctionnelle et Adaptative, Centre National la Recherche scientifique, UMR 8251, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France.
⁴ Department of Pathology, G. Pompidou European Hospital APHP-Université Paris Descartes, Paris, France.
⁵ Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, 73170 Nakhon Pathom, Thailand.
⁶ Service des Thérapies Innovantes, Institute Jacob, CEA 92265 Fontenay-aux-Roses and University Paris Saclay UMR-E007, 91405 Orsay Cedex, France; INSERM, Paris, France.
⁷ Service des Thérapies Innovantes, Institute Jacob, CEA 92265 Fontenay-aux-Roses and University Paris Saclay UMR-E007, 91405 Orsay Cedex, France; Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, 73170 Nakhon Pathom, Thailand; Genetics Division, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02215, USA.
⁸ Service des Thérapies Innovantes, Institute Jacob, CEA 92265 Fontenay-aux-Roses and University Paris Saclay UMR-E007, 91405 Orsay Cedex, France; INSERM, Paris, France. Electronic address: stany.chretien@cea.fr.

PMID: 29262331
DOI: 10.1016/j.celrep.2017.11.098

Abstract

GATA transcription factors and their FOG cofactors play a key role in tissue-specific development and differentiation, from worms to humans. Mammals have six GATA and two FOG factors. We recently demonstrated that interactions between retinoblastoma protein (pRb) and GATA-1 are crucial for erythroid proliferation and differentiation. We show here that the LXCXE pRb-binding site of FOG-2 is involved in adipogenesis. Unlike GATA-1, which inhibits cell division, FOG-2 promotes proliferation. Mice with a knockin of a Fog2 gene bearing a mutated LXCXE pRb-binding site are resistant to obesity and display higher rates of white-to-brown fat conversion. Thus, each component of the GATA/FOG complex (GATA-1 and FOG-2) is involved in pRb/E2F regulation, but these molecules have markedly different roles in the control of tissue homeostasis.

Keywords: BAT; FOG-2; GATA; WAT; adipogenesis; obesity; retinoblastoma.

MeSH terms

Adipogenesis*
Adipose Tissue, Brown / metabolism
Adipose Tissue, White / metabolism
Amino Acid Motifs
Animals
Cell Line
Cell Proliferation
DNA-Binding Proteins / chemistry
DNA-Binding Proteins / genetics
DNA-Binding Proteins / metabolism*
Mice
Mutation
Obesity / genetics*
Obesity / metabolism
Transcription Factors / chemistry
Transcription Factors / genetics
Transcription Factors / metabolism*

Substances

DNA-Binding Proteins
Transcription Factors
Zfpm2 protein, mouse