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

Summary GATA transcription factorsand their FOGcofactors play a key role in tissue-specific development and differentiation, from worms to humans. Mammals have six GATA and two FOGfactors. 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/ FOGcomplex (GATA-1 and FOG-2) is involved in pRb/ E2Fregulation, but these molecules have markedly different roles in the control of tissue homeostasis.