Barish, Grant D.Yu, Ruth T.Karunasiri, Malith S.Becerra, DianaKim, JasonTseng, Tiffany W.Tai, Li-JungLeBlanc, MatthiasDiehl, CodyCerchietti, LeandroMiller, Yury I.Witztum, Joseph L.Melnick, Ari M.Dent, Alexander L.Tangirala, Rajendra K.Evans, Ronald M.2025-07-072025-07-072012Barish GD, Yu RT, Karunasiri MS, et al. The Bcl6-SMRT/NCoR cistrome represses inflammation to attenuate atherosclerosis. Cell Metab. 2012;15(4):554-562. doi:10.1016/j.cmet.2012.02.012https://hdl.handle.net/1805/49236Chronic inflammation is a hallmark of atherosclerosis, but its transcriptional underpinnings are poorly understood. We show that the transcriptional repressor Bcl6 is an anti-inflammatory regulator whose loss in bone marrow of Ldlr(-/-) mice results in severe atherosclerosis and xanthomatous tendonitis, a virtually pathognomonic complication in patients with familial hypercholesterolemia. Disruption of the interaction between Bcl6 and SMRT or NCoR with a peptide inhibitor in vitro recapitulated atherogenic gene changes in mice transplanted with Bcl6-deficient bone marrow, pointing to these cofactors as key mediators of Bcl6 inflammatory suppression. Using ChIP-seq, we reveal the SMRT and NCoR corepressor cistromes, each consisting of over 30,000 binding sites with a nearly 50% overlap. While the complete cistromes identify a diversity of signaling pathways, the Bcl6-bound subcistromes for each corepressor are highly enriched for NF-κB-driven inflammatory and tissue remodeling genes. These results reveal that Bcl6-SMRT/NCoR complexes constrain immune responses and contribute to the prevention of atherosclerosis.en-USPublisher PolicyAtherosclerosisBone marrowInflammationMacrophagesCholesterolArticle