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

Resultado de la investigación: Articlerevisión exhaustiva

156 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Páginas (desde-hasta)361-371
Número de páginas11
PublicaciónCancer Cell
Volumen6
N.º4
DOI
EstadoPublished - oct. 2004
Publicado de forma externa

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Huella

Profundice en los temas de investigación de 'Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach'. En conjunto forman una huella única.

Citar esto