Gene Network Analysis of PPAR-γ: A Bioinformatics Approach Using STRING
Authors: S. Bag, S. Ramaiah, P. Anitha, K. M. Kumar, P. Lavanya, V. Sivasakhthi, A. Anbarasu
Abstract:
Gene networks present a graphical view at the level of gene activities and genetic functions and help us to understand complex interactions in a meaningful manner. In the present study, we have analyzed the gene interaction of PPAR-γ (peroxisome proliferator-activated receptor gamma) by search tool for retrieval of interacting genes. We find PPAR-γ is highly networked by genetic interactions with 10 genes: RXRA (retinoid X receptor, alpha), PPARGC1A (peroxisome proliferator-activated receptor gamma, coactivator 1 alpha), NCOA1 (nuclear receptor coactivator 1), NR0B2 (nuclear receptor subfamily 0, group B, member 2), HDAC3 (histone deacetylase 3), MED1 (mediator complex subunit 1), INS (insulin), NCOR2 (nuclear receptor co-repressor 2), PAX8 (paired box 8), ADIPOQ (adiponectin) and it augurs well for the fact that obesity and several other metabolic disorders are inter related.
Keywords: Gene networks, NCOA1, PPARγ, PPARGC1A, RXRA.
Digital Object Identifier (DOI): doi.org/10.5281/zenodo.1088034
Procedia APA BibTeX Chicago EndNote Harvard JSON MLA RIS XML ISO 690 PDF Downloads 4544References:
[1] A.de la Fuente, P. Brazhnik, and P. Mendes, “Linking the genes: inferring quantitative gene networks from microarray data,” Trends Genet,vol. 18, p. 395-8, 2002.
[2] AV. Antonov, HW. Mewes, “BIOREL: the benchmark resource to estimate the relevance of the gene networks,” FEBS Lett., vol. 580, p. 844-8, 2006.
[3] K. Kappler, R. Edwards, L. Glass, “Dynamics in high-dimensional model gene networks,” Signal Processing, vol. 83, p.89–798, 2003.
[4] D. Szklarczyk, A. Franceschini, M. Kuhn, M. Simonovic, A. Roth, P. Minguez., et al., “The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored,” Nucleic Acids Res., vol. 39, Database issue D561–D568, 2011
[5] A. Laszlo Barabasi, N. Gulbahce, and J. Loscalzo, “Network medicine: a network-based approach to human disease,” Nat Rev Genet., vol. 12, p.56–68, 2011.
[6] V. A. Javiya, J.A. Patel, “The role of peroxisome proliferator-activated receptors in human disease,” Indian J Pharmacol, vol. 38, p.243-253, 2006.
[7] Y. Guan and M.D. Breyer, “Peroxisome proliferator-activated receptors (PPARs): novel therapeutic targets in renal disease,” Kidney Int., vol. 60, p.14–30, 2001.
[8] J .Li, X. Zhu, and J.Y. Chen, “Building disease-specific drug-protein connectivity maps from molecular interaction networks and PubMed abstracts,” PLoS. Comput. Biol., vol. 5, e1000450, 2009.
[9] J. Mao, J. Ai, X. Zhou, M. Shenwu, M. Ong, M. Blue, J.T. Washington, X. Wang, and Y. Deng, “Transcriptomic profiles of peripheral white blood cells in type II diabetes and racial differences in expression profiles,” BMC Genomics, vol. 12, S12, 2011.
[10] H.N. Kadarmideen, L.L.G. Janss, “Population and systems genetics analyses of cortisol in pigs divergently selected for stress,” Physiol Genomics, vol.29, p. 57-65, 2007.
[11] G.M. Peloso, S. Demissie, D. Collins , D.B. Mirel , S.B. Gabriel , L.A. Cupples , S.J. Robins , E.J. Schaefer , and M.E. Brousseau , “Common genetic variation in multiple metabolic pathways influences susceptibility to low HDL-cholesterol and coronary heart disease,” J Lipid Res., vol. 51,p. 3524-32, 2010.
[12] R.T. Gampe, V.G.Montana, M.H. Lambert, A.B. Miller, R.K. Bledsoe, M.V. Milburn, S.A. Kliewer, T.M. Willson, and Xu HE, “Asymmetry in the PPARγ/RXRα crystal structure reveals the molecular basis of heterodimerization among nuclear receptors,” Mol. Cell., vol. 5, p. 545-55, 2000.
[13] D.L. Mohler, G. Shen, “The synthesis of tethered ligand dimers for PPARgamma-RXR protein heterodimers,” Org Biomol Chem., vol.4, p. 2082-7, 2006.
[14] Y. Wu, W.W. Chin, Y. Wang, T.P. Burris, “Ligand and coactivator identity determines the requirement of the charge clamp for coactivation of the peroxisome proliferator-activated receptor gamma,” J. Biol. Chem., vol. 278, p.8637-44, 2003.
[15] D. Patsouris, M. Müller, S. Kersten, “Peroxisome proliferator activated receptor ligands for the treatment of insulin resistance,” Curr Opin Investig Drugs, vol.5, p.1045-50, 2004.
[16] C. Qi, Y. Zhu, J. Pan, A.V. Yeldandi, M.S. Rao, N. Maeda, V. Subbarao, S. Pulikuri, T. Hashimoto, J.K. Reddy, “Mouse steroid receptor coactivator-1 is not essential for peroxisome proliferator-activated receptor alpha-regulated gene expression,” Proc Natl. Acad. Sci. U S A., vol.96, p.1585-90, 1999.
[17] H. Nishigori, H. Tomura, N. Tonooka, M. Kanamori, S. Yamada, K. Sho., et al., “Mutations in the small heterodimer partner gene are associated with mild obesity in Japanese subjects,” Proc Natl Acad Sci U S A., vol.98, p.575-80, 2001.
[18] D.J. Shin, T.F. Osborne, “Peroxisome proliferator-activated receptor-gamma coactivator-1alpha activation of CYP7A1 during food restriction and diabetes is still inhibited by small heterodimer partner,” J Biol Chem., vol. 283, p.15089-96, 2008.
[19] L. Fajas, V. Egler, R. Reiter, J. Hansen, K. Kristiansen, M.B. Debril, S. Miard, J.Auwerx, “The retinoblastoma-histone deacetylase 3 complex inhibits PPARgamma and adipocyte differentiation,” Dev Cell., vol.3, p.903-10, 2002.
[20] S.N. Kim, H.Y. Choi, Y.K. Kim, “Regulation of adipocyte differentiation by histone deacetylase inhibitors,” Arch. Pharm. Res., vol. 32, p.535-41, 2009.
[21] S. Surapureddi, N. Viswakarma, S. Yu, D. Guo, M.S. Rao, J.K. Reddy, “PRIC320, a transcription coactivator, isolated from peroxisome proliferator-binding protein complex,” Biochem. Biophys Res. Commun., vol.343, 535-43, 2006.
[22] K. Ge, Y.W. Cho, H. Guo, T.B. Hong, M. Guermah, M. Ito, H. Yu, M. Kalkum, R.G. Roeder, “Alternative mechanisms by which mediator subunit MED1/TRAP220 regulates peroxisome proliferator-activated receptor gamma-stimulated adipogenesis and target gene expression,” Mol .Cell. Biol., vol.28, p.1081-91, 2008
[23] B.G. Drew, A.C. Calkin, “Drug evaluation: K-111, an insulin-sensitizing peroxisome proliferator-activated receptor alpha agonist,” Curr. Opin. Investig. Drugs, vol.8, p.324-30, 2007.
[24] S. Chintharlapalli, S. Papineni, M. Konopleva, M. Andreef, I. Samudio, S. Safe, “2-Cyano-3, 12-dioxoolean-1, 9-dien-28-oic acid and related compounds inhibit growth of colon cancer cells through peroxisome proliferator-activated receptor gamma-dependent and -independent pathways,” Mol .Pharmacol., vol. 68, p.119-28, 2005.
[25] P. Castro, A.P. Rebocho, R.J. Soares, J. Magalhaes, L. Roque, V. Trovisco., et al., “PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma,” J. Clin. Endocrinol. Metab., vol. 91, p.213-20, 2006.
[26] C.M. Kusminski, P.E. Scherer, “The road from discovery to clinic: adiponectin as a biomarker of metabolic status,” Clin. Pharmacol. Ther., vol.86, p. 592-5, 2009.
[27] M.A. Jay and J. Ren, “Peroxisome proliferator-activated receptor (PPAR) in metabolic syndrome and type 2 diabetes mellitus,” Curr Diabetes Rev, vol.3, p.33-39, 2007.
[28] L. Qin, X. Chen, Y. Wu, Z. Feng, T. He, L.Wang, L. Liao, J. Xu, “Steroid receptor coactivator-1 upregulates integrin α₅ expression to promote breast cancer cell adhesion and migration,” Cancer Res., vol. 71, p.1742-51, 2011.
[29] Y. Zhang, C.H. Hagedorn, “L. Wang, Role of nuclear receptor SHP in metabolism and cancer,” Biochim Biophys Acta., vol. 1812, 893-908, 2011.
[30] C. Lahtz, G.P. Pfeifer, “Epigenetic changes of DNA repair genes in cancer,” J Mol Cell Biol., vol.3, p.51–58, 2011.
[31] A. Pugliese, D. Miceli, “The insulin gene in diabetes,” Diabetes Metab Res Rev., vol.18, p.13-25, 2002.
[32] A.G. Comuzzie, M.E. Tejero, T. Funahashi, L.J. Martin, A. Kissebah, M. Takahashi., et al. “The genes influencing adiponectin levels also influence risk factors for metabolic syndrome and type 2 diabetes,” Hum Biol., vol.79, p.191-200, 2007.
[33] J.H. Chung, H.J. Choi, S.Y. Kim, K.S. Hong, S.K. Min, M.H. Nam, C.W. Kim, H.K.Young, J.B. Seo, “Proteomic and biochemical analyses reveal the activation of unfolded protein response, ERK-1/2 and ribosomal protein S6 signaling in experimental autoimmune myocarditis rat model,” BMC Genomics, vol.12, p520, 2011.