RT Journal Article
SR Electronic
T1 Dependence of Histone Modifications and Gene Expression on DNA Hypermethylation in Cancer
JF Cancer Research
JO Cancer Res
FD American Association for Cancer Research
SP 7213
OP 7218
VO 62
IS 24
A1 Fahrner, Jill A.
A1 Eguchi, Sayaka
A1 Herman, James G.
A1 Baylin, Stephen B.
YR 2002
UL http://cancerres.aacrjournals.org/content/62/24/7213.abstract
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.