Allele pairing at Sun1-enriched domains at the nuclear periphery via T1A3 tandem DNA repeats.

Spatiotemporal 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 expressed Cth and Ttc4 genes 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 of T 1 A 3 tandem repeat sequences in genome organization and how the regulation of gene expression, at the level of individual alleles, relates to their spatial arrangement.