Mechanism of transcriptional silencing mediated by the methyl-CpG binding protein MBD4 and RET finger protein
| Project/Area Number |
17590333
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Experimental pathology
|
|---|
| Research Institution | Tohoku University |
|---|
Principal Investigator |
KONDO Emiko Tohoku University Graduate School of Medicine, Medical Technologist, 大学院医学系研究科, 臨床検査技師 (20374928)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
FUKUSHIGE Shinichi Tohoku University, Graduate School of Medicine, Associate Professor, 大学院医学系研究科, 助教授 (90192723)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2006: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 2005: ¥1,900,000 (Direct Cost: ¥1,900,000)
|
|---|
| Keywords | Gene / Regulation of expression / Transcriptional silencing / Methyl-CpG binding protein / MBD4 / RFP / メチルCpG結合蛋白MBD4 / MBD4の転写抑制活性へのRFP蛋白の関与 / RNA干渉法によるRFPノックダウン |
|---|
| Research Abstract |
Aberrant gene silencing in tumors via methylation of CpG islands in the promoter of many cancer-related genes affects virtually every step in tumor progression. In this process, the methyl-CpG binding domain (MBD) proteins play an essential role in transmitting epigenetic information to downstream regulatory proteins.
Among the five MBD proteins identified so far, MBD4 has been the only exception; it has long been thought to be a DNA repair protein. In this study, we demonstrated that MBD4 also has the ability to repress transcription through methyl-CpG sequences. MBD4 is involved in HDAC-dependent repression and directly binds to HDAC1 and corepressor SIN3A. Furthermore MBD4 specifically binds to highly methylated promoters of CDKN2A and MLH1 genes. In order to further investigate the role of MBD4 in methylation-based transcriptional repression, a yeast two-hybrid screening was performed, and the RET finger protein (RFP) was found to be one of the major proteins that interact with the transcriptional repression domain in MBD4. The effect of the MBD4-mediated transcriptional repression in methylated CDKIV2A and MLH1 promoters was extremely enhanced by the overexpression of RFP. Because RFP has been detected at high levels in a variety of tumor cell lines as well as testis, and embryos, RFP may have an important role in the enhancement of transcriptional repression through MBD proteins in tumorigenesis, spermatogenesis, and embryogenesis.
|
Report
(3 results)
Research Products
(5 results)
