GSE183764
9sCa: MSL2 is an allelic dosage sensor in mammals
Biallelic expression is important to ensure adequate mRNA levels as well as protect cells from deleterious heterozygous mutations. However, the factors determining biallelic expression at individual gene loci are unknown. Deletion of the MSL complex component MSL2 in hybrid mouse NPCs uncovers an unprecedented function for MSL2 in allelic regulation. While biallelically expressed in wildtype NPCs, a class of MSL2 targets switches from bi to monoallelic expression upon MSL2 loss. The silenced allele loses nascent transcription, accompanied by dramatic changes in local chromatin landscape such as monoallelic gain of H3K27me3 and DNA methylation. Meanwhile, active histone modifications, RNA POL II, BRD4 and KANSL3 are retained on the active allele. MSL2 targets include several sex-biased genes on autosomes as well as X-chromosomal genes that escape X inactivation. Together, the allele-specific resolution allowed us to unravel an MSL2 mediated safeguarding mechanism to promote biallelic gene expression of sexually dimorphic and dosage-sensitive genes in mammals. Overall design: Allele specific differential analysis of various sequencing data from ESCs and NPCs of female and male hybrid clones.