We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Changes in long-range rDNA-genomic interactions associate with altered RNA polymerase II gene programs during malignant transformation.
- Authors
Diesch, Jeannine; Bywater, Megan J.; Sanij, Elaine; Cameron, Donald P.; Schierding, William; Brajanovski, Natalie; Son, Jinbae; Sornkom, Jirawas; Hein, Nadine; Evers, Maurits; Pearson, Richard B.; McArthur, Grant A.; Ganley, Austen R. D.; O'Sullivan, Justin M.; Hannan, Ross D.; Poortinga, Gretchen
- 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. Jeannine Diesch et al. report the changes in rDNA chromatin state associated with cell transition into malignancy. They show that a specific transcription factor regulates this transition by altering rDNA chromatin, resulting in the reorganization of contacts between rDNA and the genome.
- Subjects
RNA polymerase II; RIBOSOMAL RNA; CHROMATIN; RNA polymerase I; TRANSCRIPTION factors
- Publication
Communications Biology, 2019, Vol 2, Issue 1, pN.PAG
- ISSN
2399-3642
- Publication type
Article
- DOI
10.1038/s42003-019-0284-y