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Single-chromosome transcriptional profiling reveals chromosomal gene expression regulation

Nature Methods volume 10, pages 246–248 (2013)Cite this article

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An Erratum to this article was published on 29 April 2013

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Abstract

We report intron chromosomal expression FISH (iceFISH), a multiplex imaging method for measuring gene expression and chromosome structure simultaneously on single chromosomes. We find substantial differences in transcriptional frequency between genes on a translocated chromosome and the same genes in their normal chromosomal context in the same cell. Correlations between genes on a single chromosome pointed toward a cis chromosome-level transcriptional interaction spanning 14.3 megabases.

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Figure 1: Unique identification of 20 loci on chromosome (chr) 19 by RNA FISH targeting introns in human foreskin fibroblasts.
Figure 2: Translocated portions of chromosome (chr) 19 display different expression patterns than intact chromosomes.
Figure 3: Identification of a pair of genes showing an intrachromosomal but not interchromosomal expression relationship.

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  • 27 March 2013

    In the version of this article initially published online, several bars in the bottom bar graph in Figure 2c are missing their fill color. The error has been corrected in the PDF and HTML versions of this article; this error did not occur in the print version.

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Acknowledgements

We thank Biosearch Technologies (especially M. Beal and R. Cook) for providing many of the reagents used in the iceFISH assay; J. Morrissette for her lab's assistance in performing the cytogenetic analysis; L. Cai, H. Youk, D. Muzzey, J. Gore, H. Maamar and O. Padovan-Merhar for insightful comments; G. Nair for discussions about statistics; and the lab of P. Sharp (Massachusetts Institute of Technology) for providing the HeLa cells. We gratefully acknowledge a University of Pennsylvania University Research Foundation pilot grant, the US National Institutes of Health Director's New Innovator Award (1DP2OD008514) and a Burroughs-Wellcome Fund Career Award at the Scientific Interface for supporting our work.

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Authors and Affiliations

  1. Department of Bioengineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Marshall J Levesque & Arjun Raj

Authors
  1. Marshall J Levesque
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  2. Arjun Raj
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Contributions

M.J.L. and A.R. conceived of the project, performed the analyses and wrote the paper. M.J.L. performed the experiments.

Corresponding authors

Correspondence to Marshall J Levesque or Arjun Raj.

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Competing interests

M.J.L. and A.R. are both listed as inventors on a patent application (PCT/US2012/023974) based on this method and receive royalties from Biosearch Technologies on related techniques for in situ hybridization.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–21 and Supplementary Discussion (PDF 3601 kb)

Supplementary Table 1

Oligonucleotides and dyes used for the iceFISH assay (TXT 17 kb)

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Levesque, M., Raj, A. Single-chromosome transcriptional profiling reveals chromosomal gene expression regulation. Nat Methods 10, 246–248 (2013). https://doi.org/10.1038/nmeth.2372

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