Shi Chi Leow, Jeremie Poschmann, Peh Gek Too, Juan Yin, Roy Joseph, Craig McFarlane, Shaillay Dogra, Asim Shabbir, Philip W. Ingham, Shyam Prabhakar, Melvin K. S. Leow, Yung Seng Lee, Kai Lyn Ng, Yap Seng Chong, Peter D. Gluckman, Walter Stünkel
The association between impaired fetal growth and postnatal development of obesity has been demonstrated before. By comparing adipocytes differentiated from Mesenchymal Stem Cells (MSCs) taken from the umbilical cord and derived from normal and growth restricted neonates, we identified the transcription factor SOX6 as a highly expressed gene only in growth restricted individuals. We found that SOX6 regulates the process of adipogenesis in vertebrate species by activating adipogenic regulators including PPARγ, C/EBPα, and MEST. We further show that SOX6 interacts with β-catenin in adipocytes suggesting an inhibition of WNT/β-catenin signaling thereby promoting adipogenesis. The upstream regulatory region of the MEST gene in MSCs from growth restricted subjects harbors hypo-methylated CpGs next to SOX6 binding motifs and we found that SOX6 binding is impaired by adjacent CpG methylation. In summary, we report that SOX6 is a novel regulator of adipogenesis synergizing with epigenetic mechanisms.