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

doi:10.1016/j.ccr.2004.08.029

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^*

^*Corresponding author for this work

Radiation Oncology

Research output: Contribution to journal › Article › peer-review

149 Scopus citations

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)
Pages (from-to)	361-371
Number of pages	11
Journal	Cancer Cell
Volume	6
Issue number	4
DOIs	https://doi.org/10.1016/j.ccr.2004.08.029
State	Published - Oct 2004

ASJC Scopus subject areas

Oncology
Cell Biology
Cancer Research

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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

Gius, David ; Cui, Hengmi ; Bradbury, C. Matthew ; Cook, John ; Smart, Dee Dee K ; Zhao, Shuping ; Young, Lynn ; Brandenburg, Sheri A. ; Hu, Yali ; Bisht, Kheem S. ; Ho, Allen S. ; Mattson, David ; Sun, Lunching ; Munson, Peter J. ; Chuang, Eric Y. ; Mitchell, James B. ; Feinberg, Andrew P. / Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach. In: Cancer Cell. 2004 ; Vol. 6, No. 4. pp. 361-371.

@article{4cc44314ec0b460691f3ba55c06bbc09,

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

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.",

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

note = "Funding Information: 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. ",

year = "2004",

month = oct,

doi = "10.1016/j.ccr.2004.08.029",

language = "English (US)",

volume = "6",

pages = "361--371",

journal = "Cancer Cell",

issn = "1535-6108",

publisher = "Cell Press",

number = "4",

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Gius, D, Cui, H, Bradbury, CM, Cook, J, Smart, DDK, Zhao, S, Young, L, Brandenburg, SA, Hu, Y, Bisht, KS, Ho, AS, Mattson, D, Sun, L, Munson, PJ, Chuang, EY, Mitchell, JB & Feinberg, AP 2004, 'Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach', Cancer Cell, vol. 6, no. 4, pp. 361-371. https://doi.org/10.1016/j.ccr.2004.08.029

Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach. / Gius, David; Cui, Hengmi; Bradbury, C. Matthew; Cook, John; Smart, Dee Dee K; Zhao, Shuping; Young, Lynn; Brandenburg, Sheri A.; Hu, Yali; Bisht, Kheem S.; Ho, Allen S.; Mattson, David; Sun, Lunching; Munson, Peter J.; Chuang, Eric Y.; Mitchell, James B.; Feinberg, Andrew P.

In: Cancer Cell, Vol. 6, No. 4, 10.2004, p. 361-371.

Research output: Contribution to journal › Article › peer-review

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T1 - Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach

AU - Gius, David

AU - Cui, Hengmi

AU - Bradbury, C. Matthew

AU - Cook, John

AU - Smart, Dee Dee K

AU - Zhao, Shuping

AU - Young, Lynn

AU - Brandenburg, Sheri A.

AU - Hu, Yali

AU - Bisht, Kheem S.

AU - Ho, Allen S.

AU - Mattson, David

AU - Sun, Lunching

AU - Munson, Peter J.

AU - Chuang, Eric Y.

AU - Mitchell, James B.

AU - Feinberg, Andrew P.

N1 - Funding Information: 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.

PY - 2004/10

Y1 - 2004/10

N2 - 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.

AB - 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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