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

Abstract

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. By developing 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 euchromatic DNA loci harboring monoalleleic genes are enriched with adenine-thymidine-rich tandem repeats, which are bound by Hnrnpd, the "molecular wrench", to localize these loci in a Hi-C-defined A compartment within the B compartment. Our results demonstrate the biological significance of T1A3 tandem repeat sequences in genome organization and how the regulation of gene expression, at the level of individual alleles, relates to their spatial arrangement.