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

被引：44

作者：

Leow, Shi Chi ^{[1
]}

Poschmann, Jeremie ^{[2
]}

Too, Peh Gek ^{[1
]}

Yin, Juan ^{[3
]}

Joseph, Roy ^{[1
]}

McFarlane, Craig ^{[1
]}

Dogra, Shaillay ^{[1
]}

Shabbir, Asim ^{[4
]}

Ingham, Philip W. ^{[3
,5
]}

Prabhakar, Shyam ^{[2
]}

Leow, Melvin K. S. ^{[1
,6
]}

Lee, Yung Seng ^{[1
,7
]}

Ng, Kai Lyn ^{[8
]}

Chong, Yap Seng ^{[1
,8
]}

Gluckman, Peter D. ^{[1
,9
]}

Stunkel, Walter ^{[1
]}

机构：

[1] ASTAR, SICS, 30 Med Dr, Singapore 117609, Singapore

[2] ASTAR, Genome Inst Singapore, Singapore 138672, Singapore

[3] Nanyang Technol Univ, Lee Kong Chian Sch Med, Singapore 636921, Singapore

[4] Natl Univ Singapore, Natl Univ Hosp, Dept Surg, Singapore 119074, Singapore

[5] ASTAR, Inst Mol & Cell Biol, Dev & Biomed Genet Lab, Singapore 138673, Singapore

[6] Tan Tock Seng Hosp, Dept Endocrinol, Singapore 308433, Singapore

[7] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Paediat, Singapore 119228, Singapore

[8] Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Obstet & Gynaecol, Singapore 119228, Singapore

[9] Univ Auckland, Liggins Inst, Auckland 1142, New Zealand

来源：

DEVELOPMENT | 2016年 / 143卷 / 06期

基金：

新加坡国家研究基金会;

关键词：

Developmental origins; Epigenetics; Fetal growth restriction; Mesenchymal stem cells; Obesity; Transcription factor; Human; Mouse; Zebrafish; INTRAUTERINE GROWTH; DNA METHYLATION; BIRTH-WEIGHT; PPAR-GAMMA; DISEASE; RISK; DIFFERENTIATION; NEWBORNS; L-SOX5; MUSCLE;

D O I：

10.1242/dev.131573

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 PPAR gamma, C/EBPa and MEST. We further show that SOX6 interacts with beta-catenin in adipocytes, suggesting an inhibition of WNT/beta-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.

引用

页码：950 / 961

页数：12

共 41 条

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