Figure 4

In silico analysis and gene expression studies suggests functional coupling between FTO and the BDNF/NTRK2-signalling pathway. Ablation of C/EBPs has been shown to reduce the expression of transcription factors Egr1, Egr2 (early growth response protein 1 and 2) and Fos (proto-oncogene c-Fos) following BDNF exposure in cultured neuronal cells [21, 39] linking BDNF-NTRK2 to gene transcription via C/EBPs. C/EBPβ is a substrate for phosphorylation by MAPK, one of three downstream pathways of BDNF-NTRK2 signalling [49, 50]. C/EBPs mediate the immediate early gene response of NTRK2-signalling. Recent findings by Wu et al. suggest FTO to attenuate epigenetic control of gene regulation via methylation of CpG-sites in C/EBPβ response elements (CEBPREs) [21]. In silico analysis, as well as expression studies, point to a functional coupling between FTO and the BDNF/NTRK2-signalling pathway, potentially mediated by the increased binding of C/EBPβ methylated response elements