Superresolution microscopy reveals linkages between ribosomal DNA on heterologous chromosomes.
Anaphase
/ drug effects
Animals
Cell Line
Cell Nucleolus
/ drug effects
Chromosomes, Human
/ metabolism
DNA Topoisomerases, Type II
/ metabolism
DNA, Ribosomal
/ metabolism
Humans
Hybrid Cells
/ drug effects
Induced Pluripotent Stem Cells
/ metabolism
Mice
Microscopy
/ methods
Pol1 Transcription Initiation Complex Proteins
/ metabolism
Polyploidy
Protein Binding
/ drug effects
Proto-Oncogene Proteins c-myc
/ metabolism
Telomerase
/ metabolism
Topoisomerase Inhibitors
/ pharmacology
Journal
The Journal of cell biology
ISSN: 1540-8140
Titre abrégé: J Cell Biol
Pays: United States
ID NLM: 0375356
Informations de publication
Date de publication:
05 08 2019
05 08 2019
Historique:
received:
30
10
2018
revised:
14
03
2019
accepted:
03
06
2019
pubmed:
5
7
2019
medline:
19
5
2020
entrez:
5
7
2019
Statut:
ppublish
Résumé
The spatial organization of the genome is enigmatic. Direct evidence of physical contacts between chromosomes and their visualization at nanoscale resolution has been limited. We used superresolution microscopy to demonstrate that ribosomal DNA (rDNA) can form linkages between chromosomes. We observed rDNA linkages in many different human cell types and demonstrated their resolution in anaphase. rDNA linkages are coated by the transcription factor UBF and their formation depends on UBF, indicating that they regularly occur between transcriptionally active loci. Overexpression of c-Myc increases rDNA transcription and the frequency of rDNA linkages, further suggesting that their formation depends on active transcription. Linkages persist in the absence of cohesion, but inhibition of topoisomerase II prevents their resolution in anaphase. We propose that linkages are topological intertwines occurring between transcriptionally active rDNA loci spatially colocated in the same nucleolar compartment. Our findings suggest that active DNA loci engage in physical interchromosomal connections that are an integral and pervasive feature of genome organization.
Identifiants
pubmed: 31270138
pii: jcb.201810166
doi: 10.1083/jcb.201810166
pmc: PMC6683752
doi:
Substances chimiques
DNA, Ribosomal
0
Pol1 Transcription Initiation Complex Proteins
0
Proto-Oncogene Proteins c-myc
0
Topoisomerase Inhibitors
0
transcription factor UBF
0
Telomerase
EC 2.7.7.49
DNA Topoisomerases, Type II
EC 5.99.1.3
Banques de données
GENBANK
['U13369']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
2492-2513Informations de copyright
© 2019 Potapova et al.
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