Early B-Cell Factor (O/E-1) Is a Promoter of Adipogenesis and Involved in Control of Genes Important for Terminal Adipocyte Differentiation

Abstract

Olf-1/early B-cell factor (O/E-1) is a transcription factor important for B-lymphocyte and neuronal gene regulation. Here we report that all three known O/E genes (O/E-1, -2, and -3) are expressed in mouse adipose tissue and are upregulated during adipocyte differentiation. Forced expression of O/E-1 in either the preadipocyte cell line 3T3-L1 or mouse embryonic fibroblasts augmented adipogenesis, and constitutive expression of O/E-1 in uncommitted NIH 3T3 fibroblasts led to initiation of adipocyte differentiation. Furthermore, a dominant negative form of O/E-1 partially suppressed 3T3-L1 adipogenesis, indicating that expression from endogenous O/E target genes is required for 3T3-L1 terminal differentiation. Thus, our data point to the importance of O/E target genes for adipocyte differentiation and suggest a novel role for O/E-1 as an initiator and stimulator of adipogenesis.

Identification of hypo- and hypermethylated genes related to atherosclerosis by a genome-wide analysis of DNA methylation

“…Analysis of knockout mice has also identified a role for EBF1 in lipid metabolism and phenotypes related to cardiovascular disease. EBF1-deficient mice manifest lipodystrophy characterized by a marked decrease in the amount of white adipose tissue, as well as an increase in yellow adipose tissue in bone marrow compared with wild-type controls (20), consistent with the notion that EBF1 participates in terminal adipocyte differentiation and the initiation of adipocyte development (21). The expression of EBF1 has previously been found to be increased in visceral fat and the atherosclerotic aortic wall (10), and polymorphisms of EBF1 have been shown to be related both to the plasma concentration of low density lipoprotein-cholesterol and to coronary atherosclerosis (11).…”

Ebf1 heterozygosity results in increased DNA damage in pro-B cells and their synergistic transformation by Pax5 haploinsufficiency

“…Here, the carboxy-terminal transactivation domain of Ebf1 was replaced by the repressor domain of the Drosophila protein engrailed. 26 Expression of Ebf1-engrailed resulted in downregulation of a large number of genes involved in DNA repair processes in 230-238 cells (supplemental Table 1). …”

Regulation of glucose transporter type 4 isoform gene expression in muscle and adipocytes

“…A dominant negative form of O/E-1 was shown to inhibit adipocyte differentiation, whereas overexpression in the 3T3-L1 preadipocytes induces adipogenesis (108), suggesting that O/E-1 gene expression is necessary to adipogenesis. The dimeric form of O/E-1 is responsible for insulin-mediated GLUT4 gene repression and O/E family and NF-1 compete for binding to the IRE of GLUT4 promoter (39).…”