PMID- 11164890 OWN - NLM STAT- MEDLINE DCOM- 20010315 LR - 20190826 IS - 0161-5890 (Print) IS - 0161-5890 (Linking) VI - 37 IP - 11 DP - 2000 Aug TI - Site A of the MCP-1 distal regulatory region functions as a transcriptional modulator through the transcription factor NF1. PG - 623-32 AB - The monocyte chemoattractant protein-1 (MCP-1) functions to recruit monocytes and macrophages to areas of inflammation and is a prototypic chemokine subjected to coordinate regulation by immunomodulatory agents. TNF mediated regulation of MCP-1 occurs through a distal regulatory region located 2.5 kb upstream of the transcriptional start site. Within this region are two NF-kB motifs that are each critical for function. Site A, located within the distal regulatory region and upstream of the kappaB elements is required for maximal induction by TNF. However, unlike the kappaB elements and other MCP-1 regulatory elements, Site A is constitutively occupied by factors in vivo. To better understand the nature of Site A function, this report identified a Site A binding protein and provides a functional analysis of the element in driving transcription. The results showed that the transcription factor NF1/CTF binds to Site A both in vitro and in vivo. While Site A has no transcriptional activity on its own, it was found to augment the transcriptional activity of a GAL4-VP16 reporter system in an orientation and position independent manner. Because NF1 is known to interact with factors that modify nucleosomes, these results suggest a unique role for Site A in regulating MCP-1 expression. FAU - Kumar, S N AU - Kumar SN AD - Department of Microbiology and Immunology, Emory University School of Medicine, 1510 Clifton Road, Atlanta, GA 30322, USA. FAU - Boss, J M AU - Boss JM LA - eng GR - CA74271/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - England TA - Mol Immunol JT - Molecular immunology JID - 7905289 RN - 0 (CCAAT-Enhancer-Binding Proteins) RN - 0 (CTF-1 transcription factor) RN - 0 (Chemokine CCL2) RN - 0 (NFI Transcription Factors) RN - 0 (Transcription Factors) SB - IM MH - 3T3 Cells MH - Animals MH - Base Sequence MH - Binding Sites MH - CCAAT-Enhancer-Binding Proteins/*physiology MH - Chemokine CCL2/chemistry/*physiology MH - *Gene Expression Regulation MH - Mice MH - Molecular Sequence Data MH - NFI Transcription Factors MH - Transcription Factors/*physiology MH - Transcription, Genetic EDAT- 2001/02/13 11:00 MHDA- 2001/03/17 10:01 CRDT- 2001/02/13 11:00 PHST- 2001/02/13 11:00 [pubmed] PHST- 2001/03/17 10:01 [medline] PHST- 2001/02/13 11:00 [entrez] AID - S0161589000000973 [pii] AID - 10.1016/s0161-5890(00)00097-3 [doi] PST - ppublish SO - Mol Immunol. 2000 Aug;37(11):623-32. doi: 10.1016/s0161-5890(00)00097-3.