Allele-level visualization of transcription and chromatin by high-throughput imaging.

The spatial arrangement of the genome within the nucleus is a pivotal aspect of cellular organization and function with implications for gene expression and regulation. While all genome organization features, such as loops, domains, and radial positioning, are nonrandom, they are characterized by a...

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Publicado en:Histochemistry & Cell Biology Vol. 162; no. 1/2; pp. 65 - 78
Autores principales: Almansour, Faisal, Keikhosravi, Adib, Pegoraro, Gianluca, Misteli, Tom
Formato: Journal Article
Publicado: Springer Nature Jul2024
Acceso en línea:Ver este registro en EBSCOhost
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      dt: Jul2024
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      pub: Springer Nature
      place: New York, New York
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        10.1007/s00418-024-02289-7
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        atl: Allele-level visualization of transcription and chromatin by high-throughput imaging.
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        au:
          Almansour, Faisal
          Keikhosravi, Adib
          Pegoraro, Gianluca
          Misteli, Tom
        affil: https://ror.org/040gcmg81 Cell Biology of Genomes, National Cancer Institute, National Institute of Health, 20892, Bethesda, MD, USA
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      ab: The spatial arrangement of the genome within the nucleus is a pivotal aspect of cellular organization and function with implications for gene expression and regulation. While all genome organization features, such as loops, domains, and radial positioning, are nonrandom, they are characterized by a high degree of single-cell variability. Imaging approaches are ideally suited to visualize, measure, and study single-cell heterogeneity in genome organization. Here, we describe two methods for the detection of DNA and RNA of individual gene alleles by fluorescence in situ hybridization (FISH) in a high-throughput format. We have optimized combined DNA/RNA FISH approaches either using simultaneous or sequential detection of DNA and nascent RNA. These optimized DNA and RNA FISH protocols were implemented in a 384-well plate format alongside automated image and data analysis and enable accurate detection of individual gene alleles and their gene expression status across a large cell population. We successfully visualized MYC and EGFR DNA and nascent RNA with allele-level resolution in multiple cell types, and we determined the radial position of active and inactive MYC and EGFR alleles. These optimized DNA/RNA detection approaches are versatile and sensitive tools for mapping of chromatin features and gene activity at the single-allele level and at high throughput.
      pubtype: Academic Journal
      doctype: Journal Article
      ougenre: Article
    language: English
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