Browsing by Author "Ni, Shuai"

Gene expression programs driven by transcription factors (TF) play pivotal roles in both normal cell differentiation and tumorigenesis. However, the links between genomic mutations and transcriptional dysregulation in gene expression profiles are largely unknown. Single nucleotide polymorphism (SNP) caused alterations in DNA-binding affinity of transcription factors are likely to be a major factor in many quantitative trait conditions, including familial predisposition to various types of diseases such as cancer. Therefore, the identification of SNPs that cause gene dysregulation by changing TF DNA-binding specificity may discover potential therapeutic cancer targets. Several transcription factors such as ERG, ETV1 and FLI1 from the ETS (E twenty-six) family are known for their oncogenic functions in prostate cancer and play pivotal roles in malignant transformation and tumor progression. Therefore, in this work, we conducted a comparative genomic study between human and mouse, focusing on the ETS family transcription factor regulated elements and identifying SNPs that can potentially affect ETS family TF DNA-binding to the enhancer elements, which, in turn, may initiate aberrant expression of genes under regulation. This analysis in combination with ChIP-seq data of ETS family members and known risk loci in prostate cancer, we define a novel ETS-regulated enhancer element that may confer prostate cancer risk. Through targeted resequencing of a 8449 bp region in 184 cases and 188 controls, we identify several novel SNPs that may impact on gene regulation underpinning prostate cancer susceptibility.