Project/Area Number |
16K18589
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Genetics/Chromosome dynamics
|
Research Institution | National Institute of Genetics |
Principal Investigator |
Amano Takanori 国立遺伝学研究所, 系統生物研究センター, 特任研究員 (20419849)
|
Project Period (FY) |
2016-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
|
Keywords | 遺伝子発現 / エンハンサー / マウス / 染色体動態 / ゲノム / 遺伝子発現制御 / インシュレーター / 形態形成 |
Outline of Final Research Achievements |
Genes and cis-regulatory elements (CREs) are interacted in a cell-type specific manner to achieve precise gene expression. Topologically associating domain (TAD) is a functional compartment in which efficient interactions of genes and CREs are allowed. Genes belonging to an identical TAD sometime share CREs or other time show differential expression. However, molecular mechanisms by which TAD controls gene regulation are still largely unknown. Limb-specific expression of Shh is regulated by an enhancer located in an intron of Lmbr1. We revealed that the upstream region of the Shh limb enhancer functions as an insulator that is involved in the differential expression of Shh and Lmbr1. Deletion of the insulator caused downregulation of Shh and upregulation of Mnx1, and limb abnormalities such as digit number reduction. Our result suggested that the novel CRE fulfills the dual roles as an insulator for Lmbr1 and Mnx1, and a facilitator for Shh expression.
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