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
Affiliations
Olivier Goupille
Service des Thérapies Innovantes, Institute Jacob, CEA 92265 Fontenay-aux-Roses and University Paris Saclay UMR-E007, 91405 Orsay Cedex, France
Tipparat Penglong
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
Zahra Kadri
Service des Thérapies Innovantes, Institute Jacob, CEA 92265 Fontenay-aux-Roses and University Paris Saclay UMR-E007, 91405 Orsay Cedex, France
Marine Granger-Locatelli
Service des Thérapies Innovantes, Institute Jacob, CEA 92265 Fontenay-aux-Roses and University Paris Saclay UMR-E007, 91405 Orsay Cedex, France
Raphaël Denis
Unité de Biologie Fonctionnelle et Adaptative, Centre National la Recherche scientifique, UMR 8251, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France
Serge Luquet
Unité de Biologie Fonctionnelle et Adaptative, Centre National la Recherche scientifique, UMR 8251, Université Paris Diderot, Sorbonne Paris Cité, 75205 Paris, France
Cécile Badoual
Department of Pathology, G. Pompidou European Hospital APHP-Université Paris Descartes, Paris, France
Suthat Fucharoen
Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol University, 73170 Nakhon Pathom, Thailand
Leila Maouche-Chrétien
Service des Thérapies Innovantes, Institute Jacob, CEA 92265 Fontenay-aux-Roses and University Paris Saclay UMR-E007, 91405 Orsay Cedex, France; INSERM, Paris, France
Philippe Leboulch
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
Stany Chrétien
Service des Thérapies Innovantes, Institute Jacob, CEA 92265 Fontenay-aux-Roses and University Paris Saclay UMR-E007, 91405 Orsay Cedex, France; INSERM, Paris, France; Corresponding author
Summary: 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. : Goupille et al. find that a mutation of the FOG-2 LXCXE pRb-binding site decreases cell proliferation and affects adipogenesis in vitro and in vivo. Fog2Rb−/Rb− mutant mice are resistant to obesity, and they present abnormal WAT/BAT conversion and lactate production. Oxamate treatment results in phenotype reversion in these mice. Keywords: FOG-2, GATA, retinoblastoma, WAT, BAT, adipogenesis, obesity
