AI Article Synopsis
- Researchers tested whether the effects of 5-aza-2'-deoxycytidine (5-aza-CdR) and DNMT knockout (which alters DNA methylation) are similar, and found they resemble those induced by Trichostatin A (TSA), not DNMT manipulation.
- 5-aza-CdR showed consistent effects on gene expression over one to five days, indicating it may affect methylation stability and chromatin structure directly.
- The study cautions that while agents stimulating gene activation through demethylation can be effective, they may also downregulate nearly as many genes, with a significant coordinated regulation observed in a cluster of metallothionein genes.
Article 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.
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| http://dx.doi.org/10.1016/j.ccr.2004.08.029 | DOI Listing |
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