Analysis of DNA methylation pattern of promoter CpG islands in idiopathic pulmonary fibrosis.
| Project/Area Number |
15390257
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Respiratory organ internal medicine
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| Research Institution | FUKUSHIMA MEDICAL UNIVERSITY |
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Principal Investigator |
HOMMA Yoshimi FUKUSHIMA MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (60192324)
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| Co-Investigator(Kenkyū-buntansha) |
MUNAKATA Mitsuru FUKUSHIMA MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (00209991)
KAMATAKI Akihisa FUKUSHIMA MEDICAL UNIVERSITY, SCHOOL OF MEDICINE, ASISTANT PROFESSOR, 医学部, 助手 (60360004)
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| Project Period (FY) |
2003 – 2004
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| Project Status |
Completed (Fiscal Year 2004)
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| Budget Amount *help |
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2004: ¥5,200,000 (Direct Cost: ¥5,200,000)
Fiscal Year 2003: ¥9,700,000 (Direct Cost: ¥9,700,000)
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| Keywords | genome / CpG island / DNA methylation / microarray / fluorescent probe / 蛍光プローブ / 細胞増殖因子 / シグナリング分子 |
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| Research Abstract |
Methylation of cytosine residues of the CpG dinucleotides constitutes the basis of an epigenetic control of gene expression in mammals. Genomic methylation patterns are of critical importance in various biological processes such as development, imprinting, and tumorigenesis. Most cytosines within CpG dinucleotides are methylated in the human genome, but some remain unmethylated in specific-GC rich loci, called CpG islands. These small stretches of DNA sequences are located in the promoter and first exon regions of 60% of human genes, and methylation of cytosine in these CpG islands is associated with loss of gene expression. Although much evidence has been accumulated to show aberrant de novo methylation in cancer, regulation of maintenance and de novo methylation in normal and other diseases is obscure. In this study, we developed a new microarray-based method to detect differences in methylation patterns of the promoter CpG of 360 genes including transcription factors and signaling molecules. Using this microarray, we analyzed genome samples derived from patients with idiopathic pulmonary fibrosis (IPF). Fluorescent probes were prepared from genome samples obtained from patients and normal donors by a methylation amplification method. After hybridization, array data was analyzed to compare the methylation states of two groups. Differences were detected at 〜25 loci, suggesting differential methylation states in patients with IPF. We, then, analyzed methylation of each CpG site of these loci by a bisulfite sequencing method, and detected several genes whose promoter CpG is hypomethylated in IPF. These results suggest a possible involvement of epigenetic factors in pathogenesis of IPF, and we examine the protein levels of these genes now.
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Report
(3 results)
Research Products
(21 results)
