YY1 stabilizes super enhancer-promoter loops and gene expression during mesenchymal stem cell aging (RNA-Seq)

Stem cell aging leads to a progressive functional decline in self-renewal and differentiation capacity. How chromatin architecture impacts the gene expression changes that underlie altered stem cell function remains to be fully understood. Here, by integrative analyses of transcriptomic, epigenomic and Hi-C data in young and old in vitro aged human mesenchymal stem cells (MSCs), we identified super enhancer (SE)-promoter pairs and delineated changes in these loops during aging. SE target genes are associated with GO categories involved in key MSC functions and are enriched among genes with altered expression during aging, suggesting that changes in SE activity contribute to the functional decline of aged MSCs. YY1 is highly enriched at promoters and SEs and is lost from these regions in old cells. Loss of YY1 from SE-promoter loops correlates with reduced Hi-C contacts, and YY1 knockdown in young cells recapitulates age-associated transcriptomic changes, particularly among SE target genes. Our analyses provide novel insights into the role of altered chromatin loops in stem cell aging and highlight the function of YY1 in maintaining super enhancer-promoter loops and promoting gene expression stability during this process.