4C-seq revealed long-range interactions of a functional enhancer at the 8q24 prostate cancer risk locus

• DOI: 10.1038/srep22462
• Publication Date: 2016-03-03T10:18:52Z
• Authors: Mingyang Cai; Sewoon Kim; Kai Wang; Peggy J. Farnham; Gerhard A. Coetzee; Wange Lu
• Keywords: FOXA1; Genome-wide Association Study

Abstract Genome-wide association studies (GWAS) have identified >100 independent susceptibility loci for prostate cancer, including the hot spot at 8q24. However, how genetic variants this locus confer disease risk hasn’t been fully characterized. Using circularized chromosome conformation capture (4C) coupled with next-generation sequencing and an enhancer 8q24 as “bait”, we genome-wide partners interacting in cell lines LNCaP C4-2B. These 4C-identified regions are distributed open nuclear compartments, featuring active histone marks (H3K4me1, H3K4me2 H3K27Ac). Transcription factors NKX3-1, FOXA1 AR (androgen receptor) tend to occupy these 4C regions. We genes located regions, found them linked positive regulation of mesenchymal proliferation C4-2B, several pathways (TGF beta signaling pathway p53 C4-2B). Common (e.g. MYC POU5F1B ) were both cancer lines. each line also had exclusive ELAC2 PTEN BRCA2 ZFHX3 In addition, BCL-2 C4-2B might contribute progression androgen-refractory cancer. Overall, our work reveals key involved onset progression.