2013 Fiscal Year Final Research Report
Genome-wide analysis of epigenomic alterations in pancreatic islets from mice under the risk of developing glucose intolerance
| Project/Area Number |
23591330
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | Research Institute, International Medical Center of Japan |
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Principal Investigator |
NAMMO Takao 独立行政法人国立国際医療研究センター, 代謝疾患研究部, 室長 (50594115)
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| Project Period (FY) |
2011 – 2013
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| Keywords | エネルギー・糖質代謝異常 / エピジェネティクス / 2型糖尿病 / 環境因子 / ヒストン修飾 / 膵ランゲルハンス島 / インスリン分泌 / 遺伝子発現 |
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| Research Abstract |
Both genetic and environmental factors play important roles in the aetiology of diabetes, although the molecular mechanisms underlying the disease remain largely unclear. These days, epigenetic regulation of gene expression, which results from changes in a chromosome without alterations in the DNA sequence, has drawn attention to the field of diabetes research. The aim of this study was to clarify the involvement of epigenetic mechanisms in the regulation of pancreatic beta-cell function and glucose metabolism by genome-wide analyses. By testing mouse models, such as diet-induced obese mice and spontaneously diabetic mice, we found the cis-regulatory regions exhibited changes in the epigenome that were characteristic for the model. Furthermore, these effects were associated with changes in the expression of overlapping or adjacent genes. In summary, these results suggest the importance of genome-wide study of epigenome for clarifying disease mechanisms and identifying new drug targets.
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[Journal Article] Pancreatic islet enhancer clusters enriched in type 2 diabetes risk-associated variants2014
Author(s)
Pasquali L, Gaulton KJ, Rodríguez-Seguí SA, Mularoni L, Miguel-Escalada I, Akerman I, Tena JJ, Morán I, Gómez-Marín C, van de Bunt M, Ponsa-Cobas J, Castro N, Nammo T, Cebola I, García-Hurtado J, Maestro MA, Pattou F, Piemonti L, Berney T, Gloyn AL, Ravassard P, Gómez-Skarmeta JL, Müller F, McCarthy MI, Ferrer J
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Journal Title
Nat Genet
Volume: 46
Pages: 136-143
DOI
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[Journal Article] Quantitative assessment of Pdx1 promoter activity in vivo using a secreted luciferase reporter system2013
Author(s)
Nishimura W, Eto K, Miki A, Goto M, Kawaguchi M, Nammo T, Udagawa H, Hiramoto M, Shimizu Y, Okamura T, Fujiwara T, Yasuda Y, Yasuda K
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Journal Title
Endocrinology
Volume: 154
Pages: 4388-4395
DOI
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[Journal Article] Humanβcell transcriptome analysis uncovers lncRNAs that are tissue-specific, dynamically regulated, and abnormally expressed in type 2 diabetes2012
Author(s)
Morán I, Akerman I, van de Bunt M, Xie R, Benazra M, Nammo T, Arnes L, NakićN, García-Hurtado J, Rodríguez-Seguí S, Pasquali L, Sauty-Colace C, Beucher A, Scharfmann R, van Arensbergen J, Johnson PR, Berry A, Lee C, Harkins T, Gmyr V, Pattou F, Kerr-Conte J, Piemonti L, Berney T, Hanley N, Gloyn AL, Sussel L, Langman L, Brayman KL, Sander M, McCarthy MI, Ravassard P, Ferrer J
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Journal Title
Cell Metab
Volume: 16
Pages: 435-448
DOI
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[Journal Article] KIF5B-RET fusions in lung adenocarcinoma2012
Author(s)
Kohno T, Ichikawa H, Totoki Y, Yasuda K, Hiramoto M, Nammo T, Sakamoto H, Tsuta K, Furuta K, Shimada Y, Iwakawa R, Ogiwara H, Oike T, Enari M, Schetter AJ, Okayama H, Haugen A, Skaug V, Chiku S, Yamanaka I, Arai Y, Watanabe S, Sekine I, Ogawa S, Harris CC, Tsuda H, Yoshida T, Yokota J, Shibata T
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Journal Title
Nat Med
Volume: 18
Pages: 375-377
DOI
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