| First Author | Barish GD | Year | 2012 |
| Journal | Cell Metab | Volume | 15 |
| Issue | 4 | Pages | 554-62 |
| PubMed ID | 22465074 | Mgi Jnum | J:184208 |
| Mgi Id | MGI:5320505 | Doi | 10.1016/j.cmet.2012.02.012 |
| Citation | Barish GD, et al. (2012) The Bcl6-SMRT/NCoR cistrome represses inflammation to attenuate atherosclerosis. Cell Metab 15(4):554-62 |
| abstractText | Chronic 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-kappaB-driven inflammatory and tissue remodeling genes. These results reveal that Bcl6-SMRT/NCoR complexes constrain immune responses and contribute to the prevention of atherosclerosis. |
