Allele-specific differential regulation of monoallelically expressed autosomal genes in the cardiac lineage

Abstract

Each mammalian autosomal gene is represented by two alleles in diploid cells. Yet, no insights have been made in regard to allele-specific regulatory mechanisms of autosomes. Here we used allele-specific single cell transcriptomic analysis to elucidate the establishment of monoallelic gene expression in the cardiac lineage. We found that monoallelically expressed autosomal genes in mESCs and mouse blastocyst cells are differentially regulated based on the genetic background of the parental alleles. However, the genetic background of the allele does not affect the establishment of monoallelic genes in differentiated cardiomyocytes. Additionally, we observed epigenetic differences between deterministic and random autosomal monoallelic genes. Moreover, we also found a greater contribution of the maternal versus paternal allele to the development and homeostasis of cardiac tissue and in cardiac health, highlighting the importance of maternal influence in male cardiac tissue homeostasis. Our findings emphasize the significance of allele- specific insights into gene regulation in development, homeostasis and disease.