| First Author | Barish GD | Year | 2010 |
| Journal | Genes Dev | Volume | 24 |
| Issue | 24 | Pages | 2760-5 |
| PubMed ID | 21106671 | Mgi Jnum | J:166755 |
| Mgi Id | MGI:4849574 | Doi | 10.1101/gad.1998010 |
| Citation | Barish GD, et al. (2010) Bcl-6 and NF-{kappa}B cistromes mediate opposing regulation of the innate immune response. Genes Dev 24(24):2760-5 |
| abstractText | In the macrophage, toll-like receptors (TLRs) are key sensors that trigger signaling cascades to activate inflammatory programs via the NF-kappaB gene network. However, the genomic network targeted by TLR/NF-kappaB activation and the molecular basis by which it is restrained to terminate activation and re-establish quiescence is poorly understood. Here, using chromatin immunoprecipitation sequencing (ChIP-seq), we define the NF-kappaB cistrome, which is comprised of 31,070 cis-acting binding sites responsive to lipopolysaccharide (LPS)-induced signaling. In addition, we demonstrate that the transcriptional repressor B-cell lymphoma 6 (Bcl-6) regulates nearly a third of the Tlr4-regulated transcriptome, and that 90% of the Bcl-6 cistrome is collapsed following Tlr4 activation. Bcl-6-deficient macrophages are acutely hypersensitive to LPS and, using comparative ChIP-seq analyses, we found that the Bcl-6 and NF-kappaB cistromes intersect, within nucleosomal distance, at nearly half of Bcl-6-binding sites in stimulated macrophages to promote opposing epigenetic modifications of the local chromatin. These results reveal a genomic strategy for controlling the innate immune response in which repressive and inductive cistromes establish a dynamic balance between macrophage quiescence and activation via epigenetically marked cis-regulatory elements. |
