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Allele-specific RNA imaging shows that allelic imbalances can arise in tissues through transcriptional bursting.

PLoS genetics | 2019

Extensive cell-to-cell variation exists even among putatively identical cells, and there is great interest in understanding how the properties of transcription relate to this heterogeneity. Differential expression from the two gene copies in diploid cells could potentially contribute, yet our ability to measure from which gene copy individual RNAs originated remains limited, particularly in the context of tissues. Here, we demonstrate quantitative, single molecule allele-specific RNA FISH adapted for use on tissue sections, allowing us to determine the chromosome of origin of individual RNA molecules in formaldehyde-fixed tissues. We used this method to visualize the allele-specific expression of Xist and multiple autosomal genes in mouse kidney. By combining these data with mathematical modeling, we evaluated models for allele-specific heterogeneity, in particular demonstrating that apparent expression from only one of the alleles in single cells can arise as a consequence of low-level mRNA abundance and transcriptional bursting.

Pubmed ID: 30625149 RIS Download

Research resources used in this publication

None found

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Associated grants

  • Agency: NIGMS NIH HHS, United States
    Id: T32 GM007170
  • Agency: NIAMS NIH HHS, United States
    Id: P30 AR069619
  • Agency: NHGRI NIH HHS, United States
    Id: T32 HG000046
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK087635
  • Agency: NHGRI NIH HHS, United States
    Id: RM1 HG007743
  • Agency: NIDDK NIH HHS, United States
    Id: R01 DK076077
  • Agency: NIEHS NIH HHS, United States
    Id: P30 ES013508
  • Agency: NIH HHS, United States
    Id: DP2 OD008514
  • Agency: NIGMS NIH HHS, United States
    Id: R37 GM051279
  • Agency: NCI NIH HHS, United States
    Id: K08 CA193915
  • Agency: NINDS NIH HHS, United States
    Id: F30 NS100595
  • Agency: NIDDK NIH HHS, United States
    Id: DP3 DK108220
  • Agency: NHLBI NIH HHS, United States
    Id: U01 HL129998
  • Agency: NIBIB NIH HHS, United States
    Id: R33 EB019767

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