This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Teferedegne, B. Articles by Boss, J. M. Search for Related Content PubMed PubMed Citation Articles by Teferedegne, B. Articles by Boss, J. M.

Mechanism of Action of a Distal NF-B-Dependent Enhancer

Belete Teferedegne, Myesha R. Green, Zhu Guo, and Jeremy M. Boss^*

Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, Georgia 30322

Received 13 February 2006/ Returned for modification 20 March 2006/ Accepted 5 May 2006

The monocyte chemoattractant protein 1 gene (MCP-1) is regulated by TNF through an NF-B-dependent distal enhancer and an Sp1-dependent promoter-proximal regulatory region. In the silent state, only the distal regulatory region is accessible to transcription factors. Upon activation by tumor necrosis factor, NF-B binds to the distal regulatory region and recruits CBP and p300. CBP and p300 recruitment led to specific histone modifications that ultimately enabled the binding of Sp1 to the proximal regulatory region. During this process, a direct interaction between the distal and proximal regulatory regions occurred. Sp1, NF-B, CBP, and p300 were required for this interaction. CBP/p300-mediated histone modifications enhanced the binding of the coactivator CARM1 to the distal regulatory region. CARM1, which is necessary for MCP-1 expression, was not required for distal-proximal region interactions, suggesting that it plays a later downstream activation event. The results describe a model in which the separation of the distal enhancer from the promoter-proximal region allows for two independent chromatin states to exist, preventing inappropriate gene activation at the promoter while at the same time allowing rapid induction through the distal regulatory region.

Present address: Rowett Research Institute, Greenburn, Bucksburn, AB21 9SB, Aberdeen, Scotland, United Kingdom.

Present address: Centers for Disease Control and Prevention, 1600 Clifton Rd., Atlanta, GA 30333.

This article has been cited by other articles:

• Wolter, S., Doerrie, A., Weber, A., Schneider, H., Hoffmann, E., von der Ohe, J., Bakiri, L., Wagner, E. F., Resch, K., Kracht, M. (2008). c-Jun Controls Histone Modifications, NF-{kappa}B Recruitment, and RNA Polymerase II Function To Activate the ccl2 Gene. Mol. Cell. Biol. 28: 4407-4423 [Abstract] [Full Text]  
• Bonofiglio, D, Qi, H, Gabriele, S, Catalano, S, Aquila, S, Belmonte, M, Ando, S (2008). Peroxisome proliferator-activated receptor {gamma} inhibits follicular and anaplastic thyroid carcinoma cells growth by upregulating p21Cip1/WAF1 gene in a Sp1-dependent manner. Endocr Relat Cancer 15: 545-557 [Abstract] [Full Text]  
• Sasaki, C. Y., Slemenda, C. F., Ghosh, P., Barberi, T. J., Longo, D. L. (2007). Traf1 Induction and Protection from Tumor Necrosis Factor by Nuclear Factor-{kappa}B p65 Is Independent of Serine 536 Phosphorylation. Cancer Res. 67: 11218-11225 [Abstract] [Full Text]  
• Sun, S., Tang, Y., Lou, X., Zhu, L., Yang, K., Zhang, B., Shi, H., Wang, C. (2007). UXT is a novel and essential cofactor in the NF-{kappa}B transcriptional enhanceosome. J. Cell Biol. 178: 231-244 [Abstract] [Full Text]  
• Palmer, M. B., Majumder, P., Green, M. R., Wade, P. A., Boss, J. M. (2007). A 3' Enhancer Controls Snail Expression in Melanoma Cells. Cancer Res. 67: 6113-6120 [Abstract] [Full Text]