Figure 2.

Possible mechanism showing the regulation of Id2 in the presence or absence of active Wnt signaling and consequently how Id2 regulates adipocyte differentiation through PPARγ. (Left) In the presence of Wnt, β-catenin cannot be phosphorylated and targeted for degradation. β-catenin translocates to the nucleus and performs two tasks: 1. Binds to the T-cell factor/lymphoid enhancer factor (TCF/LEF) family of transcription factors. TCF/LEF-β-catenin complexes bind to Wnt-response elements (WRE) in the promoters of target genes such as c-Myc and cyclin D1 leading to their transcriptional activation. Thus, active Wnt signaling promotes cell proliferation and inhibits adipocyte differentiation (46, 47). 2. β-catenin could suppress Id2 expression by directly binding to WRE at the Id2 promoter and recruits retinoic acid receptors (RARs) to the WRE at the Id2 promoter. This is followed by RAR-dependent recruitment of LSD1 demethylase, leading to a reduction in histone H3 and H4 acetylation and histone H3 K-4 methylation, resulting in Id2 transcriptional repression and impaired adipogenesis (48). (Right) The precise mechanism by which Id2 regulates PPARγ is not known. One possibility could be that in the absence of Wnt, C/EBPs might gain access to the Id2 promoter and induce its expression. Subsequently, Id2 by directly binding to an unknown factor, on one hand induces PPARγ expression and on the other hand suppresses c-Myc and cyclin D1 expression leading to cell cycle exit and adipocyte differentiation.