TY - JOUR
T1 - Changes in long-range rDNA-genomic interactions associate with altered RNA polymerase II gene programs during malignant transformation
AU - Diesch, Jeannine
AU - Bywater, Megan J.
AU - Sanij, Elaine
AU - Cameron, Donald P.
AU - Schierding, William
AU - Brajanovski, Natalie
AU - Son, Jinbae
AU - Sornkom, Jirawas
AU - Hein, Nadine
AU - Evers, Maurits
AU - Pearson, Richard B.
AU - McArthur, Grant A.
AU - Ganley, Austen R.D.
AU - O’Sullivan, Justin M.
AU - Hannan, Ross D.
AU - Poortinga, Gretchen
N1 - Publisher Copyright:
© 2019, Crown.
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85069168548&partnerID=8YFLogxK
U2 - 10.1038/s42003-019-0284-y
DO - 10.1038/s42003-019-0284-y
M3 - Article
SN - 2399-3642
VL - 2
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 39
ER -