研究会のご案内
リエゾンラボ研究会
発表内容

Title:
Transcriptional and Epigenetic Regulations of Metabolism

Takeshi Inagaki
Associate Professor
Division of Metabolic Medicine, Research Center for Advanced Science and Technology, The University of Tokyo

Abstract:
Nuclear hormone receptors are ligand-dependent transcription factors that play important roles in various physiological functions including metabolism. Our laboratory investigated the metabolic pathways of glycolipids with a focus on the transcriptional regulation by nuclear receptors. We demonstrated that nuclear receptors regulate glycolipid metabolism through the endocrine FGFs including FGF15/19 and FGF21. The transcriptional regulation by nuclear receptors requires their bonding to specific positions on the target DNA and the recruitment of co-factors. The subsequent changes in the chromatin structure and co-factor recruitment are regulated by epigenetic mechanisms which are independent of genomic sequences. As a potential link between environmental factors and metabolism, epigenetic regulation needs to be flexible and responsive to the continuous changes of environmental conditions. Histone modification is an example of epigenetic regulation. We recently discovered that mice lacking Jmjd1a, a demethylase of Histone H3K9, exhibit obesity, insulin insensitivity and hyperlipidemia. The findings suggest that histone methylation modifies gene expression in glycolipid metabolism and results in significant physiological changes.

References:
1. Inagaki T. , Tachibana M. , Magoori K. , Kudo H. , Tanaka T. , Okamura M. , Naito M. , Kodama T., Shinkai Y. , Sakai J. (2009). Obesity and Metabolic Syndrome in Histone Demethylase JHDM2a Deficient Mice . Genes to Cells. 14(8):991-1001

2. Inagaki T . , Lin V.Y., Goetz R . , Mohammadi M . , Mangelsdorf D . J . , Kliewer S . A . (2008). Inhibition of IGF-1 signaling and growth by the fasting-induced hormone FGF21. Cell Metab . 8 ( 1 ), 77 – 83

3. Inagaki T., Dutchak P., Zhao G., Ding X., Gautron L., Parameswara V., Li Y., Goetz R., Mohammadi M., Esser V., Elmquist J.K., Gerard R.D., Burgess S.C., Hammer R.E., Mangelsdorf D.J., Kliewer S.A. (2007). Endocrine regulation of the fasting response by PPAR a -mediated induction of fibroblast growth factor 21. Cell Metab. 5(6), 415-425

4. Inagaki T., Choi M., Moschetta A., Peng L., Cummins C.L., McDonald J.G., Luo G., Jones S.A., Goodwin B., Richardson J.A., Gerard R.D., Repa J.J., Mangelsdorf D.J., Kliewer S.A. (2005). Fibroblast growth factor 15 functions as an enterohepatic signal to regulate bile acid homeostasis.Cell Metab . 2(4), 217-225