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Locus specific epigenetic modalities of random allelic expression imbalance

Author

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  • Lucile Marion-Poll

    (Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934
    Directors’ research, European Molecular Biology Laboratory (EMBL))

  • Benjamin Forêt

    (Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934)

  • Dina Zielinski

    (Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934
    Institut Curie, PSL Research University, INSERM U900, Mines ParisTech)

  • Florian Massip

    (Berlin Institute for Medical Systems Biology, Max Delbrück Center for Molecular Medicine)

  • Mikael Attia

    (Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934)

  • Ava C. Carter

    (Stanford University)

  • Laurène Syx

    (Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934
    Institut Curie, PSL Research University, INSERM U900, Mines ParisTech)

  • Howard Y. Chang

    (Stanford University)

  • Anne-Valerie Gendrel

    (Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934)

  • Edith Heard

    (Institut Curie, PSL Research University, CNRS UMR3215, INSERM U934
    Directors’ research, European Molecular Biology Laboratory (EMBL)
    Collège de France)

Abstract

Most autosomal genes are thought to be expressed from both alleles, with some notable exceptions, including imprinted genes and genes showing random monoallelic expression (RME). The extent and nature of RME has been the subject of debate. Here we investigate the expression of several candidate RME genes in F1 hybrid mouse cells before and after differentiation, to define how they become persistently, monoallelically expressed. Clonal monoallelic expression is not present in embryonic stem cells, but we observe high frequencies of monoallelism in neuronal progenitor cells by assessing expression status in more than 200 clones. We uncover unforeseen modes of allelic expression that appear to be gene-specific and epigenetically regulated. This non-canonical allelic regulation has important implications for development and disease, including autosomal dominant disorders and opens up therapeutic perspectives.

Suggested Citation

  • Lucile Marion-Poll & Benjamin Forêt & Dina Zielinski & Florian Massip & Mikael Attia & Ava C. Carter & Laurène Syx & Howard Y. Chang & Anne-Valerie Gendrel & Edith Heard, 2021. "Locus specific epigenetic modalities of random allelic expression imbalance," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25630-3
    DOI: 10.1038/s41467-021-25630-3
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