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Development. 2016 Mar 15;143(6):950-61. doi: 10.1242/dev.131573. Epub 2016 Feb 18.

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

Author information

1
Singapore Institute for Clinical Sciences (SICS), Agency for Science Technology and Research (A*STAR), 30 Medical Drive, Singapore, Singapore 117609.
2
Genome Institute of Singapore, Agency for Science Technology and Research (A*STAR), Singapore, Singapore 138672.
3
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore 636921.
4
Department of Surgery, National University Hospital, National University of Singapore, Singapore 119074.
5
Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore 636921 Developmental and Biomedical Genetics Laboratory, Institute of Molecular and Cell Biology, Agency for Science Technology and Research (A*STAR), Singapore, Singapore 138673.
6
Singapore Institute for Clinical Sciences (SICS), Agency for Science Technology and Research (A*STAR), 30 Medical Drive, Singapore, Singapore 117609 Department of Endocrinology, Tan Tock Seng Hospital, Singapore, Singapore 308433.
7
Singapore Institute for Clinical Sciences (SICS), Agency for Science Technology and Research (A*STAR), 30 Medical Drive, Singapore, Singapore 117609 Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
8
Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
9
Singapore Institute for Clinical Sciences (SICS), Agency for Science Technology and Research (A*STAR), 30 Medical Drive, Singapore, Singapore 117609 Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228.
10
Singapore Institute for Clinical Sciences (SICS), Agency for Science Technology and Research (A*STAR), 30 Medical Drive, Singapore, Singapore 117609 Liggins Institute, University of Auckland, Auckland 1142, New Zealand.
11
Singapore Institute for Clinical Sciences (SICS), Agency for Science Technology and Research (A*STAR), 30 Medical Drive, Singapore, Singapore 117609 walter_stunkel@sics.a-star.edu.sg.

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.

KEYWORDS:

Developmental origins; Epigenetics; Fetal growth restriction; Human; Mesenchymal stem cells; Mouse; Obesity; Transcription factor; Zebrafish

PMID:
26893351
DOI:
10.1242/dev.131573
[Indexed for MEDLINE]
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