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Commun Biol. 2019 Jan 28;2(1):39. doi: 10.1038/s42003-019-0284-y.

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

Author information

1
Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia.
2
Josep Carreras Leukaemia Research Institute, Barcelona, 08021, Spain.
3
QIMR Berghofer Medical Research Institute, Brisbane, QLD, 4029, Australia.
4
Department of Pathology, University of Melbourne, Parkville, VIC, 3010, Australia.
5
ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University, Canberra, ACT, 2601, Australia.
6
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, 3010, Australia.
7
Liggins Institute, The University of Auckland, Auckland, 1023, New Zealand.
8
Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, VIC, Australia.
9
Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC, 3010, Australia.
10
Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, 3065, Australia.
11
School of Biological Sciences, The University of Auckland, Auckland, 1010, New Zealand.
12
Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia. ross.hannan@anu.edu.au.
13
ACRF Department of Cancer Biology and Therapeutics, John Curtin School of Medical Research, Australian National University, Canberra, ACT, 2601, Australia. ross.hannan@anu.edu.au.
14
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, 3010, Australia. ross.hannan@anu.edu.au.
15
Department of Biochemistry and Molecular Biology, Monash University, Clayton, 3800, VIC, Australia. ross.hannan@anu.edu.au.
16
Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, VIC, 3010, Australia. ross.hannan@anu.edu.au.
17
School of Biomedical Sciences, University of Queensland, Brisbane, QLD, 4072, Australia. ross.hannan@anu.edu.au.
18
Cancer Research Division, Peter MacCallum Cancer Centre, Melbourne, VIC, 3000, Australia. gretchen.poortinga@petermac.org.
19
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC, 3010, Australia. gretchen.poortinga@petermac.org.
20
Department of Medicine, St Vincent's Hospital, University of Melbourne, Fitzroy, VIC, 3065, Australia. gretchen.poortinga@petermac.org.

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.

PMID:
31924928
DOI:
10.1038/s42003-019-0284-y

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