| Project/Area Number |
14572079
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Meisei University |
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Principal Investigator |
SHIMIZU Mitsuhiro Meisei University, Faculty of Physical Sciences and Engineering, Associate Professor, 理工学部, 助教授 (80231364)
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| Project Period (FY) |
2002 – 2003
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| Project Status |
Completed (Fiscal Year 2003)
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| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2003: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | chromatin / nucleosome / DNA structure / transcriptional regulation / repetitive sequences / budding yeast / genome |
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| Research Abstract |
Gene expression in eukaryotic cells involves the interaction of proteins with DNA packaged into nucleosomes. Nucleosomes are often located at distinct positions in promoter regions to regulate transcription. Thus, the factors that influence the nucleosome positioning are essential to elucidating the mechanism of gene expression. In this project, we have examined the role of DNA structures in chromatin organization and its effect on gene expression in vivo.
1.Effect of DNA structures on nucleosome positioning in vivo.
We have examined effect of simple repeating sequences that can form alternative DNA conformations on nucleosome positioning using yeast minichromosome system. The repeating sequences are categorized into 4 groups in terms of nucleosome-promoting and nucleosome-disrupting properties.
2.Effect of chromatin alteration through DNA structures on repression in yeast genome.
In Saccharomyces cerevisiae, nucleosomes are precisely positioned in the promoters of a cell-specific genes such as STE6 and BAR1. Here, we have demonstrated that chromatin alteration by intrinsic DNA structures disrupts repression of BAR1 in genome and of STE6-lacZ reporter plasmids in a cells. Therefore, proper nucleosome positioning is essential for regulation of cell type-specific transcription and cell type identity.
3.Effect of triplet repeat sequences on chromatin organization.
We have shown that triplet repeat sequences that cause human hereditary diseases affect nucleosome organization in yeast minichromosomes. Their effect on gene expression is associated with their features on chromatin structure. The sticky DNA formation at longer GAA repeats from Friedreich's ataxia was also investigated in yeast minichromosomes.
In summary, intrinsic DNA structures play important roles in nucleosome organization in vivo. Our studies also emphasizes that chromatin alteration through DNA structures would make it possible to modulate gene expression artificially in eukaryotes.
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