Changes in long-range rDNA-genomic interactions associate with altered RNA polymerase II gene programs during malignant transformation
Diesch, Jeannine (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Bywater, M. J. (QIMR Berghofer Medical Research Institute (Brisbane, Austràlia))
Sanij, E. (Department of Pathology. University of Melbourne)
Cameron, D. P. (Sir Peter MacCallum Department of Oncology. University of Melbourne)
Schierding, W. (Liggins Institute. The University of Auckland)
Brajanovski, N. (Cancer Research Division. Peter MacCallum Cancer Centre)
Son, J. (Sir Peter MacCallum Department of Oncology. University of Melbourne)
Sornkom, J. (Sir Peter MacCallum Department of Oncology. University of Melbourne)
Hein, N. (ACRF Department of Cancer Biology and Therapeutics. John Curtin School of Medical Research. Australian National University)
Evers, M. (ACRF Department of Cancer Biology and Therapeutics. John Curtin School of Medical Research. Australian National University)
Pearson, R. B. (Department of Biochemistry and Molecular Biology. University of Melbourne)
McArthur, G. A. (St Vincent's Hospital (Sydney))
Ganley, A. R. D. (School of Biological Sciences. The University of Auckland)
O'Sullivan, J. M. (Liggins Institute. The University of Auckland)
Hannan, R. D. (School of Biomedical Sciences. University of Queensland)
Poortinga, G. (St Vincent's Hospital (Sydney))
Universitat Autònoma de Barcelona

Fecha:	2019
Resumen:	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.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; recerca ; Versió publicada
Materia:	Cell Line, Tumor ; Cell Transformation, Neoplastic ; Chromatin ; Chromatin Assembly and Disassembly ; Disease Progression ; DNA, Ribosomal ; Epistasis, Genetic ; Gene Expression Profiling ; Gene Expression Regulation ; Genes, rRNA ; Genetic Predisposition to Disease ; Genome ; Humans ; Neoplasms ; RNA Polymerase II
Publicado en:	Communications Biology, Vol. 2 Núm. 1 (january 2019) , p. 39, ISSN 2399-3642

DOI: 10.1038/s42003-019-0284-y
PMID: 30701204

14 p, 2.0 MB

El registro aparece en las colecciones:
Documentos de investigación > Documentos de los grupos de investigación de la UAB > Centros y grupos de investigación (producción científica) > Ciencias de la salud y biociencias > Institut d'Investigació en Ciencies de la Salut Germans Trias i Pujol (IGTP) > Instituto de Investigación contra la Leucemia Josep Carreras
Artículos > Artículos de investigación
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