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The transcriptional specificity of NF-?B dimers is coded within the ?B DNA response elements.

ABSTRACT: Nuclear factor ?B (NF-?B) regulates gene expression by binding to specific DNA elements, known collectively as ?B sites, that are contained within the promoters/enhancers of target genes. We found that the identity of the central base pair (bp) of ?B sites profoundly affects the transcriptional activity of NF-?B dimers. RelA dimers prefer an A/T bp at this position for optimal transcriptional activation (A/T-centric) and discriminate against G/C-centric ?B sites. The p52 homodimer, in contrast, activates transcription from G/C-centric ?B sites in complex with Bcl3 but represses transcription from the A/T-centric sites. The p52:Bcl3 complex binds to these two classes of ?B sites in distinct modes, permitting the recruitment of coactivator, corepressor, or both coactivator and corepressor complexes in promoters that contain G/C-, A/T-, or both G/C- and A/T-centric sites. Therefore, through sensing of bp differences within ?B sites, NF-?B dimers modulate biological programs by activating, repressing, and altering the expression of effector genes.

SUBMITTER: Wang VY

PROVIDER: S-EPMC4167904 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature

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The transcriptional specificity of NF-κB dimers is coded within the κB DNA response elements.

Wang Vivien Ya-Fan VY Huang Wendy W Asagiri Masataka M Spann Nathanael N Hoffmann Alexander A Glass Christopher C Ghosh Gourisankar G

Cell reports 20121011 4

Nuclear factor κB (NF-κB) regulates gene expression by binding to specific DNA elements, known collectively as κB sites, that are contained within the promoters/enhancers of target genes. We found that the identity of the central base pair (bp) of κB sites profoundly affects the transcriptional activity of NF-κB dimers. RelA dimers prefer an A/T bp at this position for optimal transcriptional activation (A/T-centric) and discriminate against G/C-centric κB sites. The p52 homodimer, in contrast, ...[more]

PMID: 23063365

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Project description:BackgroundRickettsia conorii, the causative agent of the Mediterranean spotted fever, is transmitted to humans by the bite of infected ticks Rhipicephalus sanguineus. The skin thus constitutes an important barrier for the entry and propagation of R. conorii. Given this, analysis of the survival strategies used by the bacterium within infected skin is critical for our understanding of rickettsiosis.Methodology/principal findingsHere, we report the first genome-wide analysis of R. conorii gene expression from infected human skin biopsies. Our data showed that R. conorii exhibited a striking transcript signature that is remarkably conserved across patients, regardless of genotype. The expression profiles obtained using custom Agilent microarrays were validated by quantitative RT-PCR. Within eschars, the amount of detected R. conorii transcripts was of 55%, this value being of 74% for bacteria grown in Vero cells. In such infected host tissues, approximately 15% (n = 211) of the total predicted R. conorii ORFs appeared differentially expressed compared to bacteria grown in standard laboratory conditions. These genes are mostly down-regulated and encode proteins essential for bacterial replication. Some of the strategies displayed by rickettsiae to overcome the host defense barriers, thus avoiding killing, were also pointed out. The observed up-regulation of rickettsial genes associated with DNA repair is likely to correspond to a DNA-damaging agent enriched environment generated by the host cells to eradicate the pathogens. Survival of R. conorii within eschars also involves adaptation to osmotic stress, changes in cell surface proteins and up-regulation of some virulence factors. Interestingly, in contrast to down-regulated transcripts, we noticed that up-regulated ones rather exhibit a small nucleotide size, most of them being exclusive for the spotted fever group rickettsiae.Conclusion/significanceBecause eschar is a site for rickettsial introduction, the pattern of rickettsial gene expression observed here may define how rickettsiae counteract the host defense.

Dataset Information

The transcriptional specificity of NF-?B dimers is coded within the ?B DNA response elements.

Publications

The transcriptional specificity of NF-κB dimers is coded within the κB DNA response elements.

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