Abstract
We tested the hypothesis that the effects on gene expression of altered DNA methylation by 5-aza-2′-deoxycytidine (5-aza-CdR) and genetic (DNMT knockout) manipulation of DNA are similar, and distinct from Trichostatin A (TSA)-induced chromatin decondensation. Surprisingly, the effects of 5-aza-CdR were more similar to those of TSA than to DNMT1, DNMT3B, or double DNMT somatic cell knockout. Furthermore, the effects of 5-aza-CdR were similar at one and five days exposure, suggesting active demethylation or direct influence of both drugs on the stability of methylation and/or chromatin marks. Agents that induce gene activation through hypomethylation may have unintended consequences, since nearly as many genes were downregulated as upregulated after demethylation. In addition, a 75 kb cluster of metallothionein genes was coordinately regulated.
Original language | English (US) |
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Pages (from-to) | 361-371 |
Number of pages | 11 |
Journal | Cancer cell |
Volume | 6 |
Issue number | 4 |
DOIs | |
State | Published - Oct 2004 |
Funding
We thank Ina Rhee and Bert Vogelstein for the HCT116 knockout cell lines. This work was supported by grants CA65145 (A.P.F.), CA72602 (D.G.), and CA75556 (D.G.) from the National Institutes of Health.
ASJC Scopus subject areas
- Oncology
- Cancer Research