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

被引：165

作者：

Gius, D

Cui, HM

Bradbury, CM

Cook, J

Smart, DDK

Zhao, SP

Young, L

Brandenburg, SA

Hu, YL

Bisht, KS

Ho, AS

Mattson, D

Sun, LC

Munson, PJ

Chuang, EY

Mitchell, JB

Feinberg, AP ^{[1
]}

机构：

[1] Johns Hopkins Univ, Sch Med, Inst Med Genet, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Biol Mol, Baltimore, MD 21205 USA

[4] Johns Hopkins Univ, Sch Med, Dept Genet, Baltimore, MD 21205 USA

[5] Johns Hopkins Univ, Sch Med, Ctr Oncol, Baltimore, MD 21205 USA

[6] NCI, Radiat Oncol Branch, Radiat Oncol Sci Program,Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[7] NCI, Radiat Oncol Branch, Ctr Canc Res, NIH, Bethesda, MD 20892 USA

[8] NIH, Math & Stat Comp Lab, Ctr Informat Technol, Bethesda, MD 20892 USA

来源：

CANCER CELL | 2004年 / 6卷 / 04期

关键词：

D O I：

10.1016/j.ccr.2004.08.029

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：361 / 371

页数：11

共 42 条

[1] The protein CTCF is required for the enhancer blocking activity of vertebrate insulators [J].