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Molecular and in silico characterization of a promoter module and C/EBP element that mediate LPS‐induced RANTES/CCL5 expression in monocytic cells

ABSTRACT The chemokine RANTES/CCL5 is a proinflammatory agent produced by a variety of tissues in response to specific stimuli. In human monocytes, RANTES/CCL5 transcription is up‐regulated rapidly and transiently in response to LPS. We describe here two regions that help control LPS‐driven transcri...

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Published in:The FASEB journal 2001-03, Vol.15 (3), p.577-579
Main Authors: Fessele, Sabine, Boehlk, Sabine, Mojaat, Anke, Miyamoto, Neil G., Werner, Thomas, Nelson, Edward L., Schloendorff, Detlef, Nelson, Peter J.
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cited_by cdi_FETCH-LOGICAL-c371E-92635bd46b2d1c68498a6e054b411819d47897059349a83786f57dc48c92d6193
cites cdi_FETCH-LOGICAL-c371E-92635bd46b2d1c68498a6e054b411819d47897059349a83786f57dc48c92d6193
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container_title The FASEB journal
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creator Fessele, Sabine
Boehlk, Sabine
Mojaat, Anke
Miyamoto, Neil G.
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Schloendorff, Detlef
Nelson, Peter J.
description ABSTRACT The chemokine RANTES/CCL5 is a proinflammatory agent produced by a variety of tissues in response to specific stimuli. In human monocytes, RANTES/CCL5 transcription is up‐regulated rapidly and transiently in response to LPS. We describe here two regions that help control LPS‐driven transcription from the human RANTES/CCL5 promoter in monocytic cells. These sites were analyzed by using DNase I footprinting, transient transfection assays, site‐directed mutagenesis, and EMSA. RANTES site E (R(E), ‐125/‐99) constitutively binds C/EBP proteins in monocytic Mono Mac 6 cells. Mutation of region R(E) led to a significant (40%–50%) reduction in LPS‐induced promoter reporter activity. Region R(AB) is composed of tandem κB‐like elements R(A) and R(B) (‐73/‐34). These sites working in concert act as an LPS‐responsive promoter module. R(A) constitutively binds Sp1, and Rel p50/p65 following LPS stimulation. Either factor can mediate transcriptional effects at R(A). Induced Rel p50/p50 binding to site R(B) is required for LPS regulation of RANTES/CCL5 transcription. A series of computer models based on the RANTES/CCL5 promoter were generated to represent the organization of these functional elements. The models could identify LPS‐regulated promoters in human, other vertebrate, and viral sequences in various databases.
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identifier ISSN: 0892-6638
ispartof The FASEB journal, 2001-03, Vol.15 (3), p.577-579
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1530-6860
language eng
recordid cdi_proquest_miscellaneous_17102089
source Wiley
subjects bioinformatic
C/EBP
CCAAT-Enhancer-Binding Proteins - metabolism
Cell Line
Chemokine CCL5 - genetics
Chemokine CCL5 - metabolism
Computer Simulation
Dimerization
Genes, Reporter - genetics
Humans
Lipopolysaccharides - pharmacology
LPS
monocyte
Monocytes - drug effects
Monocytes - metabolism
NF-kappa B - genetics
NF-kappa B - metabolism
Promoter Regions, Genetic - genetics
RANTES/CCL5
Rel
Sp1
Sp1 Transcription Factor - genetics
Sp1 Transcription Factor - metabolism
transcriptional‐regulation
Transfection
title Molecular and in silico characterization of a promoter module and C/EBP element that mediate LPS‐induced RANTES/CCL5 expression in monocytic cells
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