Computational and Mathematical Methods in Medicine
Volume 2012 (2012), Article ID 568950, 10 pages
http://dx.doi.org/10.1155/2012/568950
Research Article

Identification and Functional Annotation of Genome-Wide ER-Regulated Genes in Breast Cancer Based on ChIP-Seq Data

Min Ding,1,2 Haiyun Wang,2 Jiajia Chen,3 Bairong Shen,3 and Zhonghua Xu4

1Department of Viral and Gene Therapy, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University, Shanghai 200438, China
2School of Life science and Technology, Tongji University, Shanghai 200092, China
3Center for Systems Biology, Soochow University, Suzhou Jiangsu 215006, China
4Department of Cardiothoracic Surgery, Second Affiliated Hospital of Soochow University, Suzhou Jiangsu 215004, China

Received 1 November 2012; Accepted 18 December 2012

Academic Editor: Hong-Bin Shen

Copyright © 2012 Min Ding et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Estrogen receptor (ER) is a crucial molecule symbol of breast cancer. Molecular interactions between ER complexes and DNA regulate the expression of genes responsible for cancer cell phenotypes. However, the positions and mechanisms of the ER binding with downstream gene targets are far from being fully understood. ChIP-Seq is an important assay for the genome-wide study of protein-DNA interactions. In this paper, we explored the genome-wide chromatin localization of ER-DNA binding regions by analyzing ChIP-Seq data from MCF-7 breast cancer cell line. By integrating three peak detection algorithms and two datasets, we localized 933 ER binding sites, 92% among which were located far away from promoters, suggesting long-range control by ER. Moreover, 489 genes in the vicinity of ER binding sites were identified as estrogen response elements by comparison with expression data. In addition, 836 single nucleotide polymorphisms (SNPs) in or near 157 ER-regulated genes were found in the vicinity of ER binding sites. Furthermore, we annotated the function of the nearest-neighbor genes of these binding sites using Gene Ontology (GO), KEGG, and GeneGo pathway databases. The results revealed novel ER-regulated genes pathways for further experimental validation. ER was found to affect every developed stage of breast cancer by regulating genes related to the development, progression, and metastasis. This study provides a deeper understanding of the regulatory mechanisms of ER and its associated genes.