Genomic Interaction Profiles in Breast Cancer Reveal Altered Chromatin Architecture

摘要: Gene transcription can be regulated by remote enhancer regions through chromosome looping either in cis or trans. Cancer cells are characterized wholesale changes long-range gene interactions, but the role that these interactions play cancer progression and metastasis is not well understood. In this study, we used IGFBP3, a involved breast pathogenesis, as bait 4C-seq experiment comparing normal (HMEC) with two cell lines (MCF7, an ER positive line, MDA-MB-231, triple negative line). The IGFBP3 interaction profile was substantially altered cancer. Many seen lost novel appear lines. We found HMEC, carcinoma amplified sequence family (BCAS) 1–4 were among top 10 most significantly enriched of IGFBP3. 3D-FISH analysis indicated translocation-prone BCAS genes, which located on chromosomes 1, 17, 20, close physical proximity each other cells. also epidermal growth factor receptor (EGFR), implicated tumorigenesis, interacts may their regulation. Breakpoint suggests when interacting region undergoes translocation additional detectable 4C gained. Overall, our data from multiple evidence suggest important for chromosomal pathogenesis