Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach

David Gius, Hengmi Cui, C. Matthew Bradbury, John Cook, Dee Dee K. Smart, Shuping Zhao, Lynn Young, Sheri A. Brandenburg, Yali Hu, Kheem S. Bisht, Allen S. Ho, David Mattson, Lunching Sun, Peter J. Munson, Eric Y. Chuang, James B. Mitchell, Andrew P. Feinberg

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)361-371
Number of pages11
JournalCancer cell
Volume6
Issue number4
DOIs
StatePublished - Oct 1 2004

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

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  • Cite this

    Gius, D., Cui, H., Bradbury, C. M., Cook, J., Smart, D. D. K., Zhao, S., Young, L., Brandenburg, S. A., Hu, Y., Bisht, K. S., Ho, A. S., Mattson, D., Sun, L., Munson, P. J., Chuang, E. Y., Mitchell, J. B., & Feinberg, A. P. (2004). Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach. Cancer cell, 6(4), 361-371. https://doi.org/10.1016/j.ccr.2004.08.029