| Budget Amount *help |
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1998: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1997: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Research Abstract |
Promoter region of the rat aldolase B (A ldB) gene has an important role in liver-specific transcription. In addition, this DNA region has been shown to acts as an initiation region of DNA replication in cells that do not transcribe the AldB gene. In order to know significance of functional switch of this promoter/origin region during cell differentiation, we tried to determine cis-elements required for initiation of DNA replication and to characterize their roles.
We found that, firstly. the promoter/origin region has an overlapping set of cis-elements for transcription and replication. In cells in which the AldB gene is actively transcribed, repliction initiates from a region other than the promoter region. Secondly, cis-elements for replication bind proteins in a cell cycle-dependent manner. Thirdly, DNA regions that associates with nuclear matrix differed between AldB-expressing and non-expressing cells, indicating different architecture of chromosomal domain. The promoter/origin region in AldB non-expressing cells, the origin region associates with nuclear matrix, while it does not in AldB-expressing cells.
These results do not argue against our model where an array of firing origins on the chromosome tightly links the pattern of genes being transcribed, and the positional change of the firing origins are involved in changes of specific gene expression during cell differentiation. To ascertain the above possibility, positioning of firing origins should be determined within a broad range of chromosomal region encompassing the AldB promoter/origin, with respect to distribution of genes that are actively transcribed. It is also interesting to consider that association of replication origins with nuclear matrix causes alteration of chromosomal domains that leads to transcriptional regulation.
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