Changes in long-range rDNA-genomic interactions associate with altered RNA polymerase II gene programs during malignant transformation

Jeannine Diesch, Megan J. Bywater, Elaine Sanij, Donald P. Cameron, William Schierding, Natalie Brajanovski, Jinbae Son, Jirawas Sornkom, Nadine Hein, Maurits Evers, Richard B. Pearson, Grant A. McArthur, Austen R.D. Ganley, Justin M. O’Sullivan, Ross D. Hannan*, Gretchen Poortinga

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    34 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Article number39
    JournalCommunications Biology
    Volume2
    Issue number1
    DOIs
    Publication statusPublished - 1 Dec 2019

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