Journal Article

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

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

2019

Overview

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.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 14/32 / 38/23 / 42/89 / 45/91 / 631/337/100/101 / 631/337/386/1362 / 631/337/572/2102 / 631/67/69 / 64/110 / Biology / Biomedical and Life Sciences / Cell differentiation / Cell Line, Tumor / Cell survival / Cell Transformation, Neoplastic - genetics / Chromatin / Chromatin - genetics / Chromatin - metabolism / Chromatin Assembly and Disassembly / Disease Progression / DNA, Ribosomal - genetics / DNA-directed RNA polymerase / Epistasis, Genetic / Gene expression / Gene Expression Profiling / Gene Expression Regulation / Genes, rRNA / Genetic Predisposition to Disease / Genetic transformation / Genome / Genomes / Humans / Life Sciences / Lymphocytes B / Lymphoma / Malignancy / Myc protein / Neoplasms - genetics / Neoplasms - metabolism / Neoplasms - pathology / Nucleoli / RNA polymerase / RNA Polymerase II - genetics / rRNA / Transcription factors