Estrogen receptor α target genes: The role of integrated computational genomics and chromation immunoprecipitation microarray

Victor X. Jin, Yu Wei Leu, Sandya Liyanarachchi, Hao Sun, Meiyun Fan, Kenneth P. Nephew, Tim H.M. Huang, Ramana V. Davuluri

Research output: Contribution to journalArticle

Abstract

Objective - To identify these promoter sequences involve in regulating gene expression by direct or indirect methods. Design - A combination of a systematic computational approach and microaray-based ChIP-on-chip for the genome-wide identification of ERα target genes. Method - We conducted a genome-wide screening with a novel microarray technique called ChIP-on-chip. A set of 70 candidate ERα loci was identified and the corresponding promoter sequences were analysed by statistical pattern recognition and comparative genomics approaches. Results - We found mouse counterparts for 63 of these loci and classified 42 (67%) as direct ERα targets using classification and regression tree (CART) statistical model which involves position weight matrix and human-mouse sequence similarity scores as model parameters. The remaining genes were considered to be indirect targets. To validate this computational prediction, we conducted an additional ChIP-on-chip assay that identified acetylated chromatin components in active ERα promoters. Of the 27 loci upregulated in and ERα-positive breast cancer cell line, 20 having mouse counterparts were correctly predicted by CART. Discussion and Conclusion - This integrated approach, therefore, sets a paradigm in which the iterative process of model refinement and experimental verification will continue until an accurate production of promoter target sequences is derived.

Original languageEnglish (US)
Pages (from-to)64-74
Number of pages11
JournalInternational Journal of Medicine
Volume8
Issue number1
StatePublished - Dec 1 2006

Keywords

  • ChIP-on-chip
  • Estrogen receptor α
  • Gene
  • Transcription factors

ASJC Scopus subject areas

  • Medicine(all)

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    Jin, V. X., Leu, Y. W., Liyanarachchi, S., Sun, H., Fan, M., Nephew, K. P., Huang, T. H. M., & Davuluri, R. V. (2006). Estrogen receptor α target genes: The role of integrated computational genomics and chromation immunoprecipitation microarray. International Journal of Medicine, 8(1), 64-74.