Differential sensitivity of zinc finger transcription factors MTF-1, Sp1 and Krox-20 to CpG methylation of their binding sites

Details

Serval ID
serval:BIB_F7B87B7924C9
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Differential sensitivity of zinc finger transcription factors MTF-1, Sp1 and Krox-20 to CpG methylation of their binding sites
Journal
Biological Chemistry Hoppe-Seyler
Author(s)
Radtke  F., Hug  M., Georgiev  O., Matsuo  K., Schaffner  W.
ISSN
0177-3593 (Print)
Publication state
Published
Issued date
01/1996
Volume
377
Number
1
Pages
47-56
Notes
Journal Article --- Old month value: Jan
Abstract
Cytosine methylation at CpG sites is often negatively correlated with mammalian gene activity. Many transcription factors whose DNA binding site contains one or more CpG dinucleotides are no longer able to efficiently bind DNA when the site is methylated. A notable exception is the zinc finger factor Sp1 which binds DNA and activates transcription even when its binding site is methylated. Here we show that two other zinc finger factors, MTF-1 and Krox-20, can also bind to CpG methylated sites. MTF-1 regulates metallothionein gene transcription by binding to a number of metal responsive elements (MREs), and Krox-20 regulates Hox genes during hindbrain segmentation. However, a refined analysis of MTF-1/MRE binding shows that methylation is not tolerated at every binding site: the highest affinity site in the mouse metallothionein I gene, MREd, is unaffected by methylation, while two other MRE sites with CpGs at different positions are rendered partially or completely nonfunctional by methylation. Both methylation sensitive and insensitive factors/binding sites are likely to determine the developmental expression pattern of a gene.
Keywords
Animals Base Sequence Binding Sites CpG Islands DNA-Binding Proteins/genetics Early Growth Response Protein 2 Humans Methylation Mice Molecular Sequence Data Plasmids RNA/analysis Sp1 Transcription Factor/genetics Transcription Factors/*genetics Transcription, Genetic Transfection Zinc Fingers/*genetics
Pubmed
Web of science
Open Access
Yes
Create date
28/01/2008 11:39
Last modification date
20/08/2019 16:23
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