Regulation of CHD2 expression by the Chaserr long noncoding RNA gene is essential for viability.
Animals
Chromatin Assembly and Disassembly
/ genetics
DNA-Binding Proteins
/ genetics
Gene Expression Regulation
Genes, Lethal
Growth Disorders
/ genetics
Haploinsufficiency
Heterozygote
Homozygote
Mice
Mice, Knockout
Promoter Regions, Genetic
RNA, Long Noncoding
/ genetics
RNA, Messenger
/ metabolism
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
08 11 2019
08 11 2019
Historique:
received:
22
02
2019
accepted:
18
10
2019
entrez:
10
11
2019
pubmed:
11
11
2019
medline:
4
3
2020
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 31704914
doi: 10.1038/s41467-019-13075-8
pii: 10.1038/s41467-019-13075-8
pmc: PMC6841665
doi:
Substances chimiques
Chd2 protein, mouse
0
DNA-Binding Proteins
0
RNA, Long Noncoding
0
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
5092Références
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