Fig. 7: Schematic model of LLPS-mediated WDR5-NANOG interaction in transcriptional activation and pluripotency maintenance.
From: WDR5 remodels NANOG condensates to drive transcriptional programs and sustain stem cell identity
In the absence of WDR5, NANOG tends to form irregular aggregates that are less competent for productive chromatin engagement and cofactor recruitment, resulting in reduced activation of pluripotency-associated genes. Upon WDR5 binding, NANOG is remodeled into dynamic, liquid-like condensates that can co-enrich histone-modifying complexes (e.g., SET1/MLL and MOF), supporting H3K4me3 and H4K16ac at target loci and thereby promoting gene activation. Disruption of the WDR5-NANOG interaction by either the R153A mutation or C16 treatment shifts NANOG toward a less dynamic, aggregated state, thereby impairing transcriptional activation of pluripotency-associated genes. Created in BioRender. Shi, Y. (2025) https://BioRender.com/r4b9esd.
