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

被引：37

作者：

Diesch, Jeannine ^{[1
,11
]}

Bywater, Megan J. ^{[1
,12
]}

Sanij, Elaine ^{[1
,2
]}

Cameron, Donald P. ^{[1
,3
,4
]}

Schierding, William ^{[5
]}

Brajanovski, Natalie ^{[1
]}

Son, Jinbae ^{[1
,4
]}

Sornkom, Jirawas ^{[1
,4
]}

Hein, Nadine ^{[3
]}

Evers, Maurits ^{[3
]}

Pearson, Richard B. ^{[1
,4
,6
,7
]}

McArthur, Grant A. ^{[1
,4
,8
]}

Ganley, Austen R. D. ^{[9
]}

O'Sullivan, Justin M. ^{[5
]}

Hannan, Ross D. ^{[1
,3
,4
,6
,7
,10
]}

Poortinga, Gretchen ^{[1
,4
,8
]}

机构：

[1] Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic 3000, Australia

[2] Univ Melbourne, Dept Pathol, Parkville, Vic 3010, Australia

[3] Australian Natl Univ, John Curtin Sch Med Res, ACRF Dept Canc Biol & Therapeut, Canberra, ACT 2601, Australia

[4] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Parkville, Vic 3010, Australia

[5] Univ Auckland, Liggins Inst, Auckland 1023, New Zealand

[6] Monash Univ, Dept Biochem & Mol Biol, Clayton, Vic 3800, Australia

[7] Univ Melbourne, Dept Biochem & Mol Biol, Parkville, Vic 3010, Australia

[8] Univ Melbourne, St Vincents Hosp, Dept Med, Fitzroy, Vic 3065, Australia

[9] Univ Auckland, Sch Biol Sci, Auckland 1010, New Zealand

[10] Univ Queensland, Sch Biomed Sci, Brisbane, Qld 4072, Australia

[11] Josep Carreras Leukaemia Res Inst, Barcelona 08021, Spain

[12] QIMR Berghofer Med Res Inst, Brisbane, Qld 4029, Australia

来源：

COMMUNICATIONS BIOLOGY | 2019年 / 2卷 / 1期

基金：

澳大利亚国家健康与医学研究理事会; 英国医学研究理事会;

关键词：

CHROMOSOME CONFORMATION CAPTURE; RIBOSOMAL DNA; C-MYC; TRANSCRIPTIONAL REGULATION; EMERGING TARGET; 3D GENOME; CHROMATIN; ORGANIZATION; NUCLEOLUS; UBF;

D O I：

10.1038/s42003-019-0284-y

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：14

共 103 条

[1] THE C-MYC ONCOGENE DRIVEN BY IMMUNOGLOBULIN ENHANCERS INDUCES LYMPHOID MALIGNANCY IN TRANSGENIC MICE [J].