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 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
Pages (from-to)64-74
Number of pages11
JournalInternational Journal of Medicine
Volume8
Issue number1
StatePublished - 2006

Fingerprint

Genomics
Immunoprecipitation
Estrogen Receptors
Position-Specific Scoring Matrices
Genome
Genes
Statistical Models
Chromatin
Theoretical Models
Breast Neoplasms
Gene Expression
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Estrogen receptor α target genes : The role of integrated computational genomics and chromation immunoprecipitation microarray. / Jin, Victor X.; Leu, Yu Wei; Liyanarachchi, Sandya; Sun, Hao; Fan, Meiyun; Nephew, Kenneth; Huang, Tim H M; Davuluri, Ramana V.

In: International Journal of Medicine, Vol. 8, No. 1, 2006, p. 64-74.

Research output: Contribution to journalArticle

Jin, VX, Leu, YW, Liyanarachchi, S, Sun, H, Fan, M, Nephew, K, Huang, THM & Davuluri, RV 2006, 'Estrogen receptor α target genes: The role of integrated computational genomics and chromation immunoprecipitation microarray', International Journal of Medicine, vol. 8, no. 1, pp. 64-74.
Jin, Victor X. ; Leu, Yu Wei ; Liyanarachchi, Sandya ; Sun, Hao ; Fan, Meiyun ; Nephew, Kenneth ; Huang, Tim H M ; Davuluri, Ramana V. / Estrogen receptor α target genes : The role of integrated computational genomics and chromation immunoprecipitation microarray. In: International Journal of Medicine. 2006 ; Vol. 8, No. 1. pp. 64-74.
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