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

Freddy Radtke, Martin Hug, Oleg Georgiev, Koichi Matsuo, Walter Schaffner

研究成果: Article査読

30 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)47-56
ページ数10
ジャーナルBiological chemistry Hoppe-Seyler
377
1
DOI
出版ステータスPublished - 1996
外部発表はい

ASJC Scopus subject areas

  • 生化学

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