biostudies-literatureWu TNIA NIH HHSNational Institute on Aginge13765https://www.ebi.ac.uk/biostudies/studies/S-EPMC9924951biostudies-literatureUnknown22(2)Genome-wide association studies (GWAS) have validated a strong association of atherosclerosis with the CDKN2A/B locus, a locus harboring three tumor suppressor genes: p14^ARF , p15^INK4b , and p16^INK4a . Post-GWAS functional analysis reveals that CUX is a transcriptional activator of p16^INK4a via its specific binding to a functional SNP (fSNP) rs1537371 on the atherosclerosis-associated CDKN2A/B locus, regulating endothelial senescence. In this work, we characterize SATB2, another transcription factor that specifically binds to rs1537371. We demonstrate that even though both CUX1 and SATB2 are the homeodomain transcription factors, unlike CUX1, SATB2 is a transcriptional suppressor of p16^INK4a and overexpression of SATB2 competes with CUAging cellSATB2, coordinated with CUX1, regulates IL-1β-induced senescence-like phenotype in endothelial cells by fine-tuning the atherosclerosis-associated p16<sup>INK4a</sup> expression.PMC9924951R01AG065229R01 AG065229R01AG056279Li GLeers SAVasamsetti SBZou MDutta PWu TJiang DSun WDi WWu YfalseSATB2, coordinated with CUX1, regulates IL-1β-induced senescence-like phenotype in endothelial cells by fine-tuning the atherosclerosis-associated p16<sup>INK4a</sup> expression.Genome-wide association studies (GWAS) have validated a strong association of atherosclerosis with the CDKN2A/B locus, a locus harboring three tumor suppressor genes: p14^ARF , p15^INK4b , and p16^INK4a . Post-GWAS functional analysis reveals that CUX is a transcriptional activator of p16^INK4a via its specific binding to a functional SNP (fSNP) rs1537371 on the atherosclerosis-associated CDKN2A/B locus, regulating endothelial senescence. In this work, we characterize SATB2, another transcription factor that specifically binds to rs1537371. We demonstrate that even though both CUX1 and SATB2 are the homeodomain transcription factors, unlike CUX1, SATB2 is a transcriptional suppressor of p16^INK4a and overexpression of SATB2 competes with CU2023-01-01T00:00:00Z2023 Feb2026-05-28T13:32:51.282Z2024-11-20T00:46:26.586ZS-EPMC99249513663325310.1111/acel.13765