Comput Math Methods Med - Identification and functional annotation of genome-wide ER-regulated genes in breast cancer based on ChIP-Seq data.

Tópicos

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Resumo

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.

Resumo Limpo

estrogen receptor er crucial molecul symbol breast cancer molecular interact er complex dna regul express gene respons cancer cell phenotyp howev posit mechan er bind downstream gene target far fulli understood chipseq import assay genomewid studi proteindna interact paper explor genomewid chromatin local erdna bind region analyz chipseq data mcf breast cancer cell line integr three peak detect algorithm two dataset local er bind site among locat far away promot suggest longrang control er moreov gene vicin er bind site identifi estrogen respons element comparison express data addit singl nucleotid polymorph snps near erregul gene found vicin er bind site furthermor annot function nearestneighbor gene bind site use gene ontolog go kegg genego pathway databas result reveal novel erregul gene pathway experiment valid er found affect everi develop stage breast cancer regul gene relat develop progress metastasi studi provid deeper understand regulatori mechan er associ gene

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