Binary outcomes of enhancer activity underlie stable random monoallelic expression

• DOI: 10.7554/elife.74204
• Publication Date: 2022-05-26T14:01:51Z
• Authors: Djem U Kissiov; Alexander Ethell; Sean Chen; Natalie K Wolf; Chenyu Zhang; Susanna M Dang; Yeara Jo; Katrine N Madsen; Ishan Paranjpe; Angus Y Lee; Bryan Chim; Stefan A Muljo; David H Raulet
• Keywords: Enhancer RNAs

Mitotically stable random monoallelic gene expression (RME) is documented for a small percentage of autosomal genes. We developed an in vivo genetic model to study the role enhancers RME using high-resolution single-cell analysis natural killer (NK) cell receptor and enhancer deletions mouse germline. Enhancers NK genes were accessible enriched H3K27ac on silent active alleles alike cells sorted according allelic status, suggesting activation status can be decoupled. In with multiple enhancers, deletion reduced frequency, one instance converting universally expressed encoding NKG2D into gene, recapitulating all aspects including mitotic stability both states. The results support binary action, suggest that consequence general properties regulation by rather than RME-specific epigenetic program. Therefore, many perhaps may subject some degree RME. Surprisingly, this was borne out several define different major hematopoietic lineages, previously thought within those lineages: NKG2D, CD45, CD8α, Thy-1. propose intrinsically probabilistic allele property enhancer-controlled expression, representing extreme broad continuum.