The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis

Leow, Shi Chi, Poschmann, Jeremie, Too, Peh Gek, Yin, Juan, Joseph, Roy, McFarlane, Craig, Dogra, Shaillay, Shabbir, Asim, Ingham, Philip W., Prabhakar, Shyam, Leow, Melvin K.S., Lee, Yung Seng, Ng, Kai Lyn, Chong, Yap Seng, Gluckman, Peter D., and Stünkel, Walter (2016) The transcription factor SOX6 contributes to the developmental origins of obesity by promoting adipogenesis. Development, 143. pp. 950-961.

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Abstract

An association between impaired fetal growth and the postnatal development of obesity has been established. Here, 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 highly expressed only in growth-restricted individuals. We found that SOX6 regulates 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 hypomethylated 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.

Item ID: 52324
Item Type: Article (Research - C1)
ISSN: 1477-9129
Keywords: developmental origins, epigenetics, fetal growth restriction, mesenchymal stem cells, obesity, transcription factor Human, Mouse, Zebrafish
Funders: Singapore National Research Foundation (SNRF)Translational and Clinical Research (TCR) Flagship Programme (NMRC), Agency for Science Technology and Research (A*STAR)
Projects and Grants: NMRC/TCR/004-NUS/2008, NMRC/TCR/012-NUHS/2014
Date Deposited: 23 Mar 2018 05:59
FoR Codes: 06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060103 Cell Development, Proliferation and Death @ 32%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060104 Cell Metabolism @ 34%
06 BIOLOGICAL SCIENCES > 0601 Biochemistry and Cell Biology > 060111 Signal Transduction @ 34%
SEO Codes: 97 EXPANDING KNOWLEDGE > 970106 Expanding Knowledge in the Biological Sciences @ 100%
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