| Project/Area Number |
13680720
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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 |
Functional biochemistry
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| Research Institution | Fukushima Medical University School of Medicine |
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Principal Investigator |
SEKIMATA Masayuki Fukushima Medical University, School of Medicine, Lecturer, 医学部, 講師 (80250190)
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| Project Period (FY) |
2001 – 2002
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| Project Status |
Completed (Fiscal Year 2002)
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| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
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| Keywords | DNA methylation / Trascription factor / Zinc finger / Methyl CpG-binding protein / ジンクフィンガー分子 / クロマチン / ヒストン修飾 |
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| Research Abstract |
MBD2 is a member of the methyl-CpG binding protein family that plays an important role in methylated DNA silencing. We have recently identified a novel zinc finger protein, MIZF, as an MBD2-binding partner. To understand the physiological function of MIZF in MBD2-mediated gene silencing, we investigated the DNA-binding properties of MIZF and its potential target genes. Using a cyclic amplification and selection of targets technique, the DNA sequence CGGACGTT was determined as sufficient for MIZF binding. Deletion of individual zinc fingers revealed that five of the seven zinc fingers are required for DNA binding. Reporter assays demonstrated that MIZF represses transcription from the promoter including this DNA sequence. Database search indicated that a variety of human genes including Rb contain this sequence in their promoter region. MIZE actually bound to its recognition sequence within the Rb promoter and repressed the Rb transcription. These results suggest that MIZF, through its DNA-binding activity, acts as a sequence-specific transcriptional repressor likely involved in MBD2-mediated epigenetic genesilencing.
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