Oncogene-mediated alterations in chromatin conformation.

TitleOncogene-mediated alterations in chromatin conformation.
Publication TypeJournal Article
Year of Publication2012
AuthorsRickman DS, T Soong D, Moss B, Mosquera JMiguel, Dlabal J, Terry S, MacDonald TY, Tripodi J, Bunting K, Najfeld V, Demichelis F, Melnick AM, Elemento O, Rubin MA
JournalProc Natl Acad Sci U S A
Date Published2012 Jun 05
KeywordsBase Sequence, Cell Line, Chromatin Assembly and Disassembly, Chromatin Immunoprecipitation, DNA Primers, Flow Cytometry, High-Throughput Nucleotide Sequencing, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Molecular Sequence Data, Nucleic Acid Conformation, Reverse Transcriptase Polymerase Chain Reaction, Trans-Activators, Transcriptional Regulator ERG

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-RARĪ±.

Alternate JournalProc. Natl. Acad. Sci. U.S.A.
PubMed ID22615383
PubMed Central IDPMC3384175
Grant ListR01 CA104348 / CA / NCI NIH HHS / United States
R01 CA125612 / CA / NCI NIH HHS / United States
R01 CA179100 / CA / NCI NIH HHS / United States
CA125612 / CA / NCI NIH HHS / United States