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Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability

Author

Listed:
  • Aviv Rom

    (Weizmann Institute of Science)

  • Liliya Melamed

    (Weizmann Institute of Science)

  • Noa Gil

    (Weizmann Institute of Science)

  • Micah Jonathan Goldrich

    (Weizmann Institute of Science)

  • Rotem Kadir

    (Ben-Gurion University of the Negev)

  • Matan Golan

    (Weizmann Institute of Science)

  • Inbal Biton

    (Weizmann Institute of Science)

  • Rotem Ben-Tov Perry

    (Weizmann Institute of Science)

  • Igor Ulitsky

    (Weizmann Institute of Science)

Abstract

Chromodomain helicase DNA binding protein 2 (Chd2) is a chromatin remodeller implicated in neurological disease. Here we show that Chaserr, a highly conserved long noncoding RNA transcribed from a region near the transcription start site of Chd2 and on the same strand, acts in concert with the CHD2 protein to maintain proper Chd2 expression levels. Loss of Chaserr in mice leads to early postnatal lethality in homozygous mice, and severe growth retardation in heterozygotes. Mechanistically, loss of Chaserr leads to substantially increased Chd2 mRNA and protein levels, which in turn lead to transcriptional interference by inhibiting promoters found downstream of highly expressed genes. We further show that Chaserr production represses Chd2 expression solely in cis, and that the phenotypic consequences of Chaserr loss are rescued when Chd2 is perturbed as well. Targeting Chaserr is thus a potential strategy for increasing CHD2 levels in haploinsufficient individuals.

Suggested Citation

  • Aviv Rom & Liliya Melamed & Noa Gil & Micah Jonathan Goldrich & Rotem Kadir & Matan Golan & Inbal Biton & Rotem Ben-Tov Perry & Igor Ulitsky, 2019. "Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-13075-8
    DOI: 10.1038/s41467-019-13075-8
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