Superresolution microscopy reveals linkages between ribosomal DNA on heterologous chromosomes
Abstract
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.
- Authors:
-
[1];
[2];
[3];
[4]
- Stowers Institute for Medical Research, Kansas City, MO
- Institute of Medical Biology, Agency for Science, Technology and Research, Singapore
- Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA
- Stowers Institute for Medical Research, Kansas City, MO, Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE Office of Science (SC)
- OSTI Identifier:
- 1530923
- Alternate Identifier(s):
- OSTI ID: 1580897
- Grant/Contract Number:
- AC02-05CH11231
- Resource Type:
- Published Article
- Journal Name:
- Journal of Cell Biology
- Additional Journal Information:
- Journal Name: Journal of Cell Biology Journal Volume: 218 Journal Issue: 8; Journal ID: ISSN 0021-9525
- Publisher:
- Rockefeller University Press
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 59 BASIC BIOLOGICAL SCIENCES
Citation Formats
Potapova, Tamara A., Unruh, Jay R., Yu, Zulin, Rancati, Giulia, Li, Hua, Stampfer, Martha R., and Gerton, Jennifer L. Superresolution microscopy reveals linkages between ribosomal DNA on heterologous chromosomes. United States: N. p., 2019.
Web. doi:10.1083/jcb.201810166.
Potapova, Tamara A., Unruh, Jay R., Yu, Zulin, Rancati, Giulia, Li, Hua, Stampfer, Martha R., & Gerton, Jennifer L. Superresolution microscopy reveals linkages between ribosomal DNA on heterologous chromosomes. United States. doi:10.1083/jcb.201810166.
Potapova, Tamara A., Unruh, Jay R., Yu, Zulin, Rancati, Giulia, Li, Hua, Stampfer, Martha R., and Gerton, Jennifer L. Wed .
"Superresolution microscopy reveals linkages between ribosomal DNA on heterologous chromosomes". United States. doi:10.1083/jcb.201810166.
@article{osti_1530923,
title = {Superresolution microscopy reveals linkages between ribosomal DNA on heterologous chromosomes},
author = {Potapova, Tamara A. and Unruh, Jay R. and Yu, Zulin and Rancati, Giulia and Li, Hua and Stampfer, Martha R. and Gerton, Jennifer L.},
abstractNote = {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.},
doi = {10.1083/jcb.201810166},
journal = {Journal of Cell Biology},
number = 8,
volume = 218,
place = {United States},
year = {2019},
month = {7}
}
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DOI: 10.1083/jcb.201810166
DOI: 10.1083/jcb.201810166
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