Dependence of histone modifications and gene expression on DNA hypermethylation in cancer

Jill Ann Fahrner, Sayaka Eguchi, James G. Herman, Stephen B Baylin

Research output: Contribution to journalArticle

Abstract

We examined the relationship between aberrant DNA hypermethylation and key histone code components at a hypermethylated, silenced tumor suppressor gene promoter in human cancer. In lower eukaryotes, methylated H3-lysine 9 (methyl-H3-K9) determines DNA methylation and correlates with repressed gene transcription. Here we show that a zone of deacetylated histone H3 plus methyl-H3-K9 surrounds a hypermethylated, silenced hMLH1 promoter, which, when unmethylated and active, is embedded in methyl-H3-K4 and acetylated H3. Inhibiting DNA methyltransferases, but not histone deacetylases, leads first to promoter demethylation, second to gene reexpression, and finally to complete histone code reversal. Our findings suggest a new paradigm-DNA methylation may directly, or indirectly by inhibiting transcription, maintain key repressive elements of the histone code at a hypermethylated gene promoter in cancer.

Original languageEnglish (US)
Pages (from-to)7213-7218
Number of pages6
JournalCancer Research
Volume62
Issue number24
StatePublished - Dec 15 2002

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Histone Code
DNA Methylation
Gene Expression
DNA
Genes
Neoplasms
Histone Deacetylases
Methyltransferases
Tumor Suppressor Genes
Eukaryota
Histones
Lysine

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. / Fahrner, Jill Ann; Eguchi, Sayaka; Herman, James G.; Baylin, Stephen B.

In: Cancer Research, Vol. 62, No. 24, 15.12.2002, p. 7213-7218.

Research output: Contribution to journalArticle

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