2001 Fiscal Year Final Research Report Summary
The mechanism of transcriptional repression by the nuclear hormone receptor in the preceuse of hormones by using vitamin D receptor as a model system
| Project/Area Number |
11470224
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Endocrinology
|
|---|
| Research Institution | The University of Tokyo |
|---|
Principal Investigator |
OKAZAKI Tomoki The University of Tokyo, Facaulty of Medicine, Associate Professor, 医学部附属病院, 助教授 (60203973)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KATO Shigeaki Institute of Molecular Cellular Biology, Professor, 分子細胞生物学研究所, 教授 (60204468)
|
|---|
| Project Period (FY) |
1999 – 2001
|
| Keywords | Vitamin D receptor / Transcriptional Repression / HDAC / Chromatin Immunoprecipitation / Estrogen Receptor / nVDRE |
|---|
| Research Abstract |
By introducing the negative vitamin response element (nVDRE) in the PTHrP gene into the cultured cells, we obtained the following results. 1) Chromatin immunoprecipitation (ChIP) assay revealed that vitamin D recruited VDR (vitamin D receptor) and HDAC2 (histone deacetylase 2) to the nVDRE-containing chromatin both in the transfected and endogenous PTHrP genes. 2) HDAC1, acetylated histone3 (AcH3) and acetylated histone 4 (AcH4) were recruited to the nVDRE region only in the absence of vitamin D. These results together with our experiments using a HDAC inhibitor suggested vitamin D repressed the expression of the nVDRE-containing gene through deacetylation of the chromatin surrounding the nVDRE region. 3) In the subsequent immunoprecipitation assay, we found that VDR interacted with HDAC2 in a vitamin D-dependent manner. 4) Further, we also found that estrogen recruited estrogen receptor and HDAC2 to the same nVDRE-containing chromatin region by using similar ChIP assay. Likewise, HDAC1, AcH3 and AcH4 were recruited only in the absence of estrogen. These results suggest that there exists a common machinery for negative gene regulation by the liganded nuclear hormone receptors.
|
Research Products
(8 results)
