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

Nat Commun. 2019; 
Rom A, Melamed L, Gil N, Goldrich MJ, Kadir R, Golan M, Biton I, Perry RB, Ulitsky I.
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摘要

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 Chaser... More

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