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

O Goupille (1) , T Penglong (1, 2) , Z Kadri (1) , M Granger-Locatelli (1) , R Denis (3) , S Luquet (3) , C Badoual (4, 5) , S Fucharoen (2) , L Maouche-Chretien (1) , P Leboulch (1, 2, 6, 7) , S Chretien (1)

1 JACOB - Institut de Biologie François JACOB
2 Mahidol University [Bangkok]
3 BFA (UMR_8251 / U1133) - Unité de Biologie Fonctionnelle et Adaptative
4 HEGP - Hôpital Européen Georges Pompidou [APHP]
5 UPD5 - Université Paris Descartes - Paris 5
6 Brigham and Women's Hospital [Boston]
7 HMS - Harvard Medical School [Boston]

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: GATA TRANSCRIPTION FACTORS; ZINC-FINGER PROTEINS; DIET-INDUCED OBESITY; ENERGY-EXPENDITURE; ADIPOSE-TISSUE; BROWN FAT; LACTATE; DIFFERENTIATION; WHITE; EXPRESSION

Domains: Life Sciences [q-bio]

O Goupille, T Penglong, Z Kadri, M Granger-Locatelli, R Denis, et al.. The LXCXE Retinoblastoma Protein-Binding Motif of FOG-2 Regulates Adipogenesis. Cell Reports, 2017, 21 (12), pp.3524-3535. ⟨10.1016/j.celrep.2017.11.098⟩. ⟨hal-03108274⟩