Decreasing <i>Wapl</i> dosage partially corrects embryonic growth and brain transcriptome phenotypes in <i>Nipbl^+/-</i> embryos.

ABSTRACT: Cohesin rings interact with DNA and modulate the expression of thousands of genes. NIPBL loads cohesin onto chromosomes, and WAPL takes it off. Haploinsufficiency for NIPBL causes a developmental disorder, Cornelia de Lange syndrome (CdLS), that is modeled by Nipbl^+/- mice. Mutations in WAPL have not been shown to cause disease or gene expression changes in mammals. Here, we show dysregulation of >1000 genes in Wapl^Δ/+ embryonic mouse brain. The patterns of dysregulation are highly similar in Wapl and Nipbl heterozygotes, suggesting that Wapl mutations may also cause human disease. Since WAPL and NIPBL have opposite effects on cohesin's association with DNA, we asked whether decreasing Wapl dosage could co

SUBMITTER: Kean CM 

PROVIDER: S-EPMC9710879 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature