YY1 in hematopoietic stem cells: epigenetic regulation, chromatin architecture, and aging

Yin Yang 1 (YY1) is a multifunctional transcription factor (TF) with established roles in lymphocyte development. More recently, its functions as a Polycomb group (PcG) protein and chromatin structural regulator in the hematopoietic system have gained increasing attention. This mini-review summarizes emerging insights into the epigenetic and architectural roles of YY1 in fetal and adult hematopoietic stem cells (HSCs), extending beyond its classical transcriptional activity. We also discuss how altered YY1 function contributes to HSC aging and hematopoietic decline.

Recent studies show that YY1 is essential for maintaining HSC quiescence, self-renewal, and engraftment during both fetal and adult hematopoiesis. Mechanistically, YY1 regulates hematopoiesis through PcG-dependent pathways and by shaping higher-order chromatin organization. It mediates long-range chromatin interactions, cooperates with cohesin and CTCF to organize three-dimensional genome architecture, and coordinates transcriptional and metabolic programs critical for stem cell maintenance. Notably, age-associated reductions in YY1 activity are linked to functional impairment of HSCs, implicating YY1 in hematopoietic aging.

YY1 acts as a TF, chromatin organizer, and PcG protein in hematopoiesis. Defining its roles in normal and aging HSCs may reveal mechanisms of hematopoietic decline and inform strategies to preserve blood system function.