Allele pairing at Sun1-enriched domains at the nuclear periphery viaT1A3tandem DNA repeats

Abstract

AbstractSpatiotemporal gene regulation is fundamental to the biology of diploid cells. Therefore, effective communication between two alleles and their geometry in the nucleus is important. However, the mechanism that fine-tunes the expression from each of the two alleles of an autosome is enigmatic. Establishing an allele-specific gene expression visualization system in living cells, we show that alleles of biallelically expressedCthandTtc4genes are paired prior to acquiring monoallelic expression. We found that active alleles of monoallelic genes are preferentially localized at Sun1-enriched domains at the nuclear periphery. These peripherally localized active DNA loci are enriched with adenine-thymidine-rich tandem repeats that interact with Hnrnpd and reside in a Hi-C-defined A compartment within the B compartment. Our results demonstrate the biological significance ofT1A3tandem repeat sequences in genome organization and how the regulation of gene expression, at the level of individual alleles, relates to their spatial arrangement.