In:
Nature Communications, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2019-11-08)
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.
Type of Medium:
Online Resource
ISSN:
2041-1723
DOI:
10.1038/s41467-019-13075-8
Language:
English
Publisher:
Springer Science and Business Media LLC
Publication Date:
2019
detail.hit.zdb_id:
2553671-0
