Distinct effects on gene expression of chemical and genetic manipulation of the cancer epigenome revealed by a multimodality approach
| Autor: | Lynn Young, Eric Y. Chuang, Sheri A. Brandenburg, Lunching Sun, Peter J. Munson, Allen S. Ho, C. Matthew Bradbury, Hengmi Cui, Shuping Zhao, Yali Hu, Kheem S. Bisht, David Gius, John A. Cook, Dee Dee K. Smart, James B. Mitchell, David M. Mattson, Andrew P. Feinberg |
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| Rok vydání: | 2004 |
| Předmět: |
DNA (Cytosine-5-)-Methyltransferase 1
Transcriptional Activation Cancer Research Apoptosis Biology Decitabine Hydroxamic Acids Epigenesis Genetic Cell Line Tumor Neoplasms medicine Cluster Analysis Humans DNA (Cytosine-5-)-Methyltransferases Gene Silencing RNA Messenger Promoter Regions Genetic Gene neoplasms Oligonucleotide Array Sequence Analysis Regulation of gene expression Genome Reproducibility of Results Methylation Epigenome Cell Biology Methyltransferases DNA Methylation Molecular biology Chromatin Gene Expression Regulation Neoplastic Trichostatin A Oncology DNA methylation DNMT1 Azacitidine Metallothionein Algorithms Cell Division medicine.drug |
| Zdroj: | Cancer cell. 6(4) |
| ISSN: | 1535-6108 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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