The Bcl6-SMRT/NCoR cistrome represses inflammation to attenuate atherosclerosis Academic Article uri icon

Overview

MeSH Major

  • Atherosclerosis
  • DNA-Binding Proteins
  • Inflammation
  • Nuclear Receptor Co-Repressor 2

abstract

  • 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.

publication date

  • April 4, 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3367511

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2012.02.012

PubMed ID

  • 22465074

Additional Document Info

start page

  • 554

end page

  • 62

volume

  • 15

number

  • 4