Apr 25
Binary outcomes of enhancer action underlie stable random monoallelic expression
Djem Kissiov '12 will present on research at Raulet Laboratory, UC Berkeley.
Autosomal genes are generally co-expressed from both alleles. Notable exceptions include genomic imprinting, allelic exclusion of the T and B cell receptor genes, and the stochastic and monoallelic expression of olfactory receptor genes. In recent years random and monoallelic gene expression (RME) has been documented in mammalian genomes, and surprisingly may describe up to 10% of all genes expressed in a given tissue. In vivo CRISPR/Cas9 deletion of enhancers of the RME natural killer (NK) cell receptor genes in the mouse germline revealed that enhancers primarily regulate the probability of target gene expression (rather than expression level per cell), in line with the previously proposed binary model of enhancer action. The results suggested that, rather than an exception, RME might be a consequence of general and stochastic properties of gene regulation. In support of this model, genes whose expression was previously considered to be lineage-defining in various hematopoietic lineages were found to display rare but bona fide RME. The potentially ubiquitous nature of RME has broad implications for both development and disease.