Journal
COMMUNICATIONS BIOLOGY
Volume 2, Issue -, Pages -Publisher
NATURE PORTFOLIO
DOI: 10.1038/s42003-019-0284-y
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Funding
- National Health and Medical Research Council (NHMRC) of Australia
- Cancer Council of Victoria
- Leukaemia Foundation of Australia
- NHMRC
- Sir Edward Weary Dunlop fellowship
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The three-dimensional organization of the genome contributes to its maintenance and regulation. While chromosomal regions associate with nucleolar ribosomal RNA genes (rDNA), the biological significance of rDNA-genome interactions and whether they are dynamically regulated during disease remain unclear. rDNA chromatin exists in multiple inactive and active states and their transition is regulated by the RNA polymerase I transcription factor UBTF. Here, using a MYC-driven lymphoma model, we demonstrate that during malignant progression the rDNA chromatin converts to the open state, which is required for tumor cell survival. Moreover, this rDNA transition co-occurs with a reorganization of rDNA-genome contacts which correlate with gene expression changes at associated loci, impacting gene ontologies including B-cell differentiation, cell growth and metabolism. We propose that UBTF-mediated conversion to open rDNA chromatin during malignant transformation contributes to the regulation of specific gene pathways that regulate growth and differentiation through reformed long-range physical interactions with the rDNA.
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