| The Bcl6-SMRT/NCoR cistrome represses inflammation to attenuate atherosclerosis. | |
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MedLine Citation:
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PMID: 22465074 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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-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. |
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Authors:
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Grant D Barish; Ruth T Yu; Malith S Karunasiri; Diana Becerra; Jason Kim; Tiffany W Tseng; Li-Jung Tai; Matthias Leblanc; Cody Diehl; Leandro Cerchietti; Yury I Miller; Joseph L Witztum; Ari M Melnick; Alexander L Dent; Rajendra K Tangirala; Ronald M Evans |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-03-29 |
Journal Detail:
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Title: Cell metabolism Volume: 15 ISSN: 1932-7420 ISO Abbreviation: Cell Metab. Publication Date: 2012 Apr |
Date Detail:
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Created Date: 2012-05-11 Completed Date: 2012-11-13 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 101233170 Medline TA: Cell Metab Country: United States |
Other Details:
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Languages: eng Pagination: 554-62 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 Elsevier Inc. All rights reserved. |
Affiliation:
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Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA 92037, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GEO/GSE27060 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Atherosclerosis / complications, genetics*, pathology* Base Sequence Bone Marrow / drug effects, metabolism Cholesterol / metabolism DNA-Binding Proteins / genetics, metabolism* Gene Expression Regulation / drug effects Inflammation / complications, genetics*, pathology Lipoproteins, LDL / pharmacology Macrophages / drug effects, metabolism, pathology Male Mice Mice, Inbred C57BL Molecular Sequence Data Nuclear Receptor Co-Repressor 2 / genetics, metabolism* Tendinopathy / pathology |
| Grant Support | |
ID/Acronym/Agency:
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CA014195-38/CA/NCI NIH HHS; K08 HL092298/HL/NHLBI NIH HHS; K08HL092298/HL/NHLBI NIH HHS; P01 HL088093/HL/NHLBI NIH HHS; P01HL088093/HL/NHLBI NIH HHS; P30 CA014195/CA/NCI NIH HHS; P30DK063491/DK/NIDDK NIH HHS; R01 CA104348/CA/NCI NIH HHS; R01 HD027183/HD/NICHD NIH HHS; R01HD027183/HD/NICHD NIH HHS; R01HL086566/HL/NHLBI NIH HHS; R37 DK057978/DK/NIDDK NIH HHS; R37DK057978/DK/NIDDK NIH HHS; U19 DK062434/DK/NIDDK NIH HHS; U19DK062434/DK/NIDDK NIH HHS; //Howard Hughes Medical Institute; //Howard Hughes Medical Institute |
| Chemical | |
Reg. No./Substance:
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0/Bcl6 protein, mouse; 0/DNA-Binding Proteins; 0/Lipoproteins, LDL; 0/Ncor2 protein, mouse; 0/Nuclear Receptor Co-Repressor 2; 0/oxidized low density lipoprotein; 57-88-5/Cholesterol |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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