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Title: Genome-wide Mapping of RELA(p65) Binding Identifies E2F1 as a Transcriptional Activator Recruited by NF-κB upon TLR4 Activation
Authors: Lim, C.-A.
Yao, F.
Wong, J.J.-Y.
George, J.
Xu, H.
Chiu, K.P.
Sung, W.-K. 
Lipovich, L.
Vega, V.B.
Chen, J.
Shahab, A.
Zhao, X.D.
Hibberd, M.
Wei, C.-L.
Lim, B.
Ng, H.-H. 
Ruan, Y.
Chin, K.-C.
Keywords: DNA
Issue Date: 17-Aug-2007
Citation: Lim, C.-A., Yao, F., Wong, J.J.-Y., George, J., Xu, H., Chiu, K.P., Sung, W.-K., Lipovich, L., Vega, V.B., Chen, J., Shahab, A., Zhao, X.D., Hibberd, M., Wei, C.-L., Lim, B., Ng, H.-H., Ruan, Y., Chin, K.-C. (2007-08-17). Genome-wide Mapping of RELA(p65) Binding Identifies E2F1 as a Transcriptional Activator Recruited by NF-κB upon TLR4 Activation. Molecular Cell 27 (4) : 622-635. ScholarBank@NUS Repository.
Abstract: NF-κB is a key mediator of inflammation. Here, we mapped the genome-wide loci bound by the RELA subunit of NF-κB in lipopolysaccharide (LPS)-stimulated human monocytic cells, and together with global gene expression profiling, found an overrepresentation of the E2F1-binding motif among RELA-bound loci associated with NF-κB target genes. Knockdown of endogenous E2F1 impaired the LPS inducibility of the proinflammatory cytokines CCL3(MIP-1α), IL23A(p19), TNF-α, and IL1-β. Upon LPS stimulation, E2F1 is rapidly recruited to the promoters of these genes along with p50/RELA heterodimer via a mechanism that is dependent on NF-κB activation. Together with the observation that E2F1 physically interacts with p50/RELA in LPS-stimulated cells, our findings suggest that NF-κB recruits E2F1 to fully activate the transcription of NF-κB target genes. Global gene expression profiling subsequently revealed a spectrum of NF-κB target genes that are positively regulated by E2F1, further demonstrating the critical role of E2F1 in the Toll-like receptor 4 pathway. © 2007 Elsevier Inc. All rights reserved.
Source Title: Molecular Cell
ISSN: 10972765
DOI: 10.1016/j.molcel.2007.06.038
Appears in Collections:Staff Publications

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