PMID- 16847329 OWN - NLM STAT- MEDLINE DCOM- 20060919 LR - 20181113 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 26 IP - 15 DP - 2006 Aug TI - Mechanism of action of a distal NF-kappaB-dependent enhancer. PG - 5759-70 AB - The monocyte chemoattractant protein 1 gene (MCP-1) is regulated by TNF through an NF-kappaB-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-kappaB 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-kappaB, 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. FAU - Teferedegne, Belete AU - Teferedegne B AD - Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA. FAU - Green, Myesha R AU - Green MR FAU - Guo, Zhu AU - Guo Z FAU - Boss, Jeremy M AU - Boss JM LA - eng GR - R01 CA096810/CA/NCI NIH HHS/United States GR - CA96810/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Chemokine CCL2) RN - 0 (Chromatin) RN - 0 (NF-kappa B) RN - 0 (RNA, Small Interfering) RN - 0 (Sp1 Transcription Factor) RN - 0 (Transcription Factor RelA) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 2.1.1.319 (Protein-Arginine N-Methyltransferases) RN - EC 2.1.1.319 (coactivator-associated arginine methyltransferase 1) RN - EC 2.3.1.48 (p300-CBP Transcription Factors) SB - IM MH - Animals MH - Chemokine CCL2/genetics/*metabolism MH - Chromatin/chemistry/metabolism MH - *Enhancer Elements, Genetic MH - Gene Expression Regulation MH - Genes, Reporter MH - Mice MH - NF-kappa B/*genetics/metabolism MH - NIH 3T3 Cells MH - Protein Structure, Tertiary MH - Protein-Arginine N-Methyltransferases/genetics/metabolism MH - RNA, Small Interfering/genetics/metabolism MH - Sp1 Transcription Factor/genetics/metabolism MH - Transcription Factor RelA/genetics/metabolism MH - Transcriptional Activation MH - Tumor Necrosis Factor-alpha/metabolism MH - p300-CBP Transcription Factors/genetics/metabolism PMC - PMC1592769 EDAT- 2006/07/19 09:00 MHDA- 2006/09/20 09:00 PMCR- 2007/02/01 CRDT- 2006/07/19 09:00 PHST- 2006/07/19 09:00 [pubmed] PHST- 2006/09/20 09:00 [medline] PHST- 2006/07/19 09:00 [entrez] PHST- 2007/02/01 00:00 [pmc-release] AID - 26/15/5759 [pii] AID - 0271-06 [pii] AID - 10.1128/MCB.00271-06 [doi] PST - ppublish SO - Mol Cell Biol. 2006 Aug;26(15):5759-70. doi: 10.1128/MCB.00271-06.