Project/Area Number |
10672137
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Human genetics
|
Research Institution | National Institute of Genetics (1999) Kyushu University (1998) |
Principal Investigator |
SASAKI Hiroyuki National Institute of Genetics, Department of Integrated Genetics, Professor, 総合遺伝研究系, 教授 (30183825)
|
Project Period (FY) |
1998 – 1999
|
Project Status |
Completed (Fiscal Year 1999)
|
Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥2,000,000 (Direct Cost: ¥2,000,000)
|
Keywords | genomic imprinting / genome domain / boundary element / insulator / transgenic mouse / enhancer / エンハンサー / ゲノムドメイン / ゲノム刷り込み |
Research Abstract |
Imprinted genes of mammals are clustered at certain regions of the genome and forms "imprinted genome domains". However, it is unknown how each imprinted domain is defined or delimited. We investigated the structure and function of the centromeric boundary (H19-L23mrp intergenic region) of the large imprinted domain on distal chromosome 7, and obtained the following results. 1 . A non-imprinted transcripts with no large ORF (Nctc 1) was identified in the intergenic region. 2. A sequence comparison between human and mouse revealed ten evolutionarily conserved segments, and seven of these worked as tissue-specific enhancers in transgenic mice. 3. Since L23mrp does not utilize the enhancers in vivo, we linked an L23mrp transgene to the enhancers and examined whether the enhancers can activate the L23mrp promoter in transgenic mice. However, the activity of the promoter itself was too high to assess the effect of the enhancers on the promoter. 4. The presence of non-coding transcripts and the clustered organization of the enhancers resembled the locus control region (LCR) of the globin locus. Since the globin LCR is known to contain a boundary element or an insulator, it is possible that a similar mechanism operates in this boundary region.
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