Abstract A31: ERG-mediated alterations in chromatin conformation

Abstract

Abstract Emerging evidence suggests that chromatin adopts a non-random three dimensional (3D) topology and that the organization of genes into structural hubs and domains affects their transcriptional status. How chromatin conformation changes in diseases such as cancer is poorly understood. Moreover, how oncogenic transcription factors, which bind to thousands of sites across the genome, influence gene regulation by globally altering the topology of chromatin requires further elucidation. To address these questions, we performed unbiased high-resolution mapping of intra- and inter-chromosome interactions upon over-expression of ERG, an oncogenic transcription factor frequently over-expressed in prostate cancer as a result of a gene fusion. By integrating data from genome-wide chromosome conformation capture (Hi-C), ERG binding (ChIP-seq), gene expression (RNA-seq) and spectral karytopying, we demonstrate for the first time that the oncogenic transcription factor ERG can induce global, reproducible and functionally coherent changes in chromatin organization that are associated with gene expression differences and genomic alterations. The results presented here have broader implications, as many driving genetic lesions in other cancer types involve altered levels of transcription factors due to genomic alterations (e.g. EWS-FLI1, c-Myc, n-Myc, PML-RARα). Citation Format: David S. Rickman, Ari Melnick, Olivier Elemento, Mark Rubin, T. David Soong, Benjamin Moss, Juan Miguel Mosquera, Jan Dlabal, Stephane Terry, Theresa MacDonald, Karen Bunting, Francesca Demichelis. ERG-mediated alterations in chromatin conformation [abstract]. In: Proceedings of the AACR Special Conference on Advances in Prostate Cancer Research; 2012 Feb 6-9; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2012;72(4 Suppl):Abstract nr A31.