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