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

Abstract

© 2017 The Author(s) 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.