Unknown,Transcriptomics,Genomics,Proteomics

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Bcl6 and NFkB cistromes mediate opposing reulation of the innate immune response


ABSTRACT: Here, using ChIP-seq, we define the NF-κB cistrome which is comprised of 31,070 cis-acting binding sites responsive to 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 lipopolysaccharide (LPS) and, using comparative ChIP-seq analyses, we find that the Bcl-6 and NF-κB 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. keywords: Genome-wide location analysis Identification of BCL6 and NFkB binding sites in unstimulated and LPS-stimulated primary bone-marrow derived macrophages.

ORGANISM(S): Mus musculus

SUBMITTER: Ruth Yu 

PROVIDER: E-GEOD-16723 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Bcl-6 and NF-kappaB cistromes mediate opposing regulation of the innate immune response.

Barish Grant D GD   Yu Ruth T RT   Karunasiri Malith M   Ocampo Corinne B CB   Dixon Jesse J   Benner Chris C   Dent Alexander L AL   Tangirala Rajendra K RK   Evans Ronald M RM  

Genes & development 20101124 24


In the macrophage, toll-like receptors (TLRs) are key sensors that trigger signaling cascades to activate inflammatory programs via the NF-κB gene network. However, the genomic network targeted by TLR/NF-κB 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-κB cistrome, which is comprised of 31,070 cis-acting binding sites responsiv  ...[more]

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