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Title: 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]; ORCiD logo [1];  [1]; ORCiD logo [2];  [1]; ORCiD logo [3]; ORCiD logo [4]
  1. Stowers Institute for Medical Research, Kansas City, MO
  2. Institute of Medical Biology, Agency for Science, Technology and Research, Singapore
  3. Biological Systems and Engineering Division, Lawrence Berkeley National Laboratory, Berkeley, CA
  4. Stowers Institute for Medical Research, Kansas City, MO, Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, KS
Publication Date:
Sponsoring Org.:
USDOE
OSTI Identifier:
1530923
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 ID: ISSN 0021-9525
Publisher:
Rockefeller University Press
Country of Publication:
United States
Language:
English

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 = ,
volume = ,
place = {United States},
year = {2019},
month = {7}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record
DOI: 10.1083/jcb.201810166

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Works referenced in this record:

Expression of the telomerase catalytic subunit, hTERT, induces resistance to transforming growth factor β growth inhibition in p16INK4A(−) human mammary epithelial cells
journal, April 2001

  • Stampfer, M. R.; Garbe, J.; Levine, G.
  • Proceedings of the National Academy of Sciences, Vol. 98, Issue 8, p. 4498-4503
  • DOI: 10.1073/pnas.071483998