Triple analysis of the cancer epigenome: An integrated microarray system for assessing gene expression, DNA methylation, and histone acetylation

Huidong Shi, Susan H. Wei, Yu Wei Leu, Farahnaz Rahmatpanah, Joseph C. Liu, Pearlly S. Yan, Kenneth Nephew, Tim Hui Ming Huang

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

We developed a novel microarray system to assess gene expression, DNA methylation, and histone acetylation in parallel, and to dissect the complex hierarchy of epigenetic changes in cancer. An integrated microarray panel consisting of 1507 short CpG island tags located at the 5′-end regions (including the first exons) was used to assess effects of epigenetic treatments on a human epithelial ovarian cancer cell line. Treatment with methylation (5-aza-2′-deoxycytidine) or deacetylation (trichostatin A) inhibitors alone resulted in up-regulation of 1.9 or 1.1% of the genes analyzed; however, the combined treatment resulted in synergistic reactivation of more genes (10.4%; P < 0.001 versus either treatment alone). On the basis of either primary or secondary responses to the treatments, genes were identified as methylation-dependent or -independent. Synergistic reactivation of the methylation-dependent genes by 5-aza-2′-deoxycytidine plus trichostatin A revealed a functional interaction between methylated promoters and deacetylated histones. Increased expression of some methylation-independent genes was associated with enhanced histone acetylation, but up-regulation of most of the genes identified using this technology was because of events downstream of the epigenetic cascade. We demonstrate proof of principle for using the triple microarray system in analyzing the dynamic relationship between transcription factors and promoter targets in cancer genomes.

Original languageEnglish
Pages (from-to)2164-2171
Number of pages8
JournalCancer Research
Volume63
Issue number9
StatePublished - May 1 2003

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DNA Methylation
Acetylation
Histones
decitabine
Gene Expression
Methylation
trichostatin A
Epigenomics
Genes
Neoplasms
Up-Regulation
CpG Islands
Exons
Transcription Factors
Genome
Technology
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Shi, H., Wei, S. H., Leu, Y. W., Rahmatpanah, F., Liu, J. C., Yan, P. S., ... Huang, T. H. M. (2003). Triple analysis of the cancer epigenome: An integrated microarray system for assessing gene expression, DNA methylation, and histone acetylation. Cancer Research, 63(9), 2164-2171.

Triple analysis of the cancer epigenome : An integrated microarray system for assessing gene expression, DNA methylation, and histone acetylation. / Shi, Huidong; Wei, Susan H.; Leu, Yu Wei; Rahmatpanah, Farahnaz; Liu, Joseph C.; Yan, Pearlly S.; Nephew, Kenneth; Huang, Tim Hui Ming.

In: Cancer Research, Vol. 63, No. 9, 01.05.2003, p. 2164-2171.

Research output: Contribution to journalArticle

Shi, H, Wei, SH, Leu, YW, Rahmatpanah, F, Liu, JC, Yan, PS, Nephew, K & Huang, THM 2003, 'Triple analysis of the cancer epigenome: An integrated microarray system for assessing gene expression, DNA methylation, and histone acetylation', Cancer Research, vol. 63, no. 9, pp. 2164-2171.
Shi, Huidong ; Wei, Susan H. ; Leu, Yu Wei ; Rahmatpanah, Farahnaz ; Liu, Joseph C. ; Yan, Pearlly S. ; Nephew, Kenneth ; Huang, Tim Hui Ming. / Triple analysis of the cancer epigenome : An integrated microarray system for assessing gene expression, DNA methylation, and histone acetylation. In: Cancer Research. 2003 ; Vol. 63, No. 9. pp. 2164-2171.
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