title: Oncogene-mediated alterations in chromatin conformation.
abstract: Emerging evidence suggests that chromatin adopts a nonrandom 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 investigation. To address these questions, we performed unbiased high-resolution mapping of intra- and interchromosome interactions upon overexpression of ERG, an oncogenic transcription factor frequently overexpressed in prostate cancer as a result of a gene fusion. By integrating data from genome-wide chromosome conformation capture (Hi-C), ERG binding, and gene expression, we demonstrate that oncogenic transcription factor overexpression is associated with global, reproducible, and functionally coherent changes in chromatin organization. The results presented here have broader implications, as genomic alterations in other cancer types frequently give rise to aberrant transcription factor expression, e.g., EWS-FLI1, c-Myc, n-Myc, and PML-RARα.
authors.affiliation: Department of Pathology and Laboratory Medicine, HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY 10065, USA.
authors.forename: David S
authors.initials: DS
authors.lastname: Rickman
authors.forename: T David
authors.initials: TD
authors.lastname: Soong
authors.forename: Benjamin
authors.initials: B
authors.lastname: Moss
authors.forename: Juan Miguel
authors.initials: JM
authors.lastname: Mosquera
authors.forename: Jan
authors.initials: J
authors.lastname: Dlabal
authors.forename: Stéphane
authors.initials: S
authors.lastname: Terry
authors.forename: Theresa Y
authors.initials: TY
authors.lastname: MacDonald
authors.forename: Joseph
authors.initials: J
authors.lastname: Tripodi
authors.forename: Karen
authors.initials: K
authors.lastname: Bunting
authors.forename: Vesna
authors.initials: V
authors.lastname: Najfeld
authors.forename: Francesca
authors.initials: F
authors.lastname: Demichelis
authors.forename: Ari M
authors.initials: AM
authors.lastname: Melnick
authors.forename: Olivier
authors.initials: O
authors.lastname: Elemento
authors.forename: Mark A
authors.initials: MA
authors.lastname: Rubin
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D042002:Chromatin Assembly and Disassembly / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators / Q000378:metabolism*; D000071230:Transcriptional Regulator ERG
chemical_list: D017931:DNA Primers; C072312:ERG protein, human; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG