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

First Author  Rom A Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  5092
PubMed ID  31704914 Mgi Jnum  J:281371
Mgi Id  MGI:6377791 Doi  10.1038/s41467-019-13075-8
Citation  Rom A, et al. (2019) Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability. Nat Commun 10(1):5092
abstractText  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.
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