PT  - JOURNAL ARTICLE
AU  - Fahrner, Jill A.
AU  - Eguchi, Sayaka
AU  - Herman, James G.
AU  - Baylin, Stephen B.
TI  - Dependence of Histone Modifications and Gene Expression on DNA Hypermethylation in Cancer
DP  - 2002 Dec 15
TA  - Cancer Research
PG  - 7213--7218
VI  - 62
IP  - 24
4099  - http://cancerres.aacrjournals.org/content/62/24/7213.short
4100  - http://cancerres.aacrjournals.org/content/62/24/7213.full
SO  - Cancer Res2002 Dec 15; 62
AB  - 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. ©2002 American Association for Cancer Research.