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A NF-κB-Dependent Dual Promoter-Enhancer Initiates the Lipopolysaccharide-Mediated Transcriptional Activation of the Chicken Lysozyme in Macrophages

The transcriptional activation of the chicken lysozyme gene (cLys) by lipopolysaccharide (LPS) in macrophages is dependent on transcription of a LPS-Inducible Non-Coding RNA (LINoCR) triggering eviction of the CCCTC-binding factor (CTCF) from a negative regulatory element upstream of the lysozyme tr...

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Autores principales: Witham, James, Ouboussad, Lylia, Lefevre, Pascal F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606415/
https://www.ncbi.nlm.nih.gov/pubmed/23533622
http://dx.doi.org/10.1371/journal.pone.0059389
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author Witham, James
Ouboussad, Lylia
Lefevre, Pascal F.
author_facet Witham, James
Ouboussad, Lylia
Lefevre, Pascal F.
author_sort Witham, James
collection PubMed
description The transcriptional activation of the chicken lysozyme gene (cLys) by lipopolysaccharide (LPS) in macrophages is dependent on transcription of a LPS-Inducible Non-Coding RNA (LINoCR) triggering eviction of the CCCTC-binding factor (CTCF) from a negative regulatory element upstream of the lysozyme transcription start site. LINoCR is transcribed from a promoter originally characterized as a hormone response enhancer in the oviduct. Herein, we report the characterization of this cis-regulatory element (CRE). In activated macrophages, a 60 bp region bound by NF-κB, AP1 and C/EBPβ controls this CRE, which is strictly dependent on NF-κB binding for its activity in luciferase assays. Moreover, the serine/threonine kinase IKKα, known to be recruited by NF-κB to NF-κB-dependent genes is found at the CRE and within the transcribing regions of both cLys and LINoCR. Such repartition suggests a simultaneous promoter and enhancer activity of this CRE, initiating cLys transcriptional activation and driving CTCF eviction. This recruitment was transient despite persistence of both cLys transcription and NF-κB binding to the CRE. Finally, comparing cLys with other LPS-inducible genes indicates that IKKα detection within transcribing regions can be correlated with the presence of the elongating form of RNA polymerase II or concentrated in the 3′ end of the gene.
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spelling pubmed-36064152013-03-26 A NF-κB-Dependent Dual Promoter-Enhancer Initiates the Lipopolysaccharide-Mediated Transcriptional Activation of the Chicken Lysozyme in Macrophages Witham, James Ouboussad, Lylia Lefevre, Pascal F. PLoS One Research Article The transcriptional activation of the chicken lysozyme gene (cLys) by lipopolysaccharide (LPS) in macrophages is dependent on transcription of a LPS-Inducible Non-Coding RNA (LINoCR) triggering eviction of the CCCTC-binding factor (CTCF) from a negative regulatory element upstream of the lysozyme transcription start site. LINoCR is transcribed from a promoter originally characterized as a hormone response enhancer in the oviduct. Herein, we report the characterization of this cis-regulatory element (CRE). In activated macrophages, a 60 bp region bound by NF-κB, AP1 and C/EBPβ controls this CRE, which is strictly dependent on NF-κB binding for its activity in luciferase assays. Moreover, the serine/threonine kinase IKKα, known to be recruited by NF-κB to NF-κB-dependent genes is found at the CRE and within the transcribing regions of both cLys and LINoCR. Such repartition suggests a simultaneous promoter and enhancer activity of this CRE, initiating cLys transcriptional activation and driving CTCF eviction. This recruitment was transient despite persistence of both cLys transcription and NF-κB binding to the CRE. Finally, comparing cLys with other LPS-inducible genes indicates that IKKα detection within transcribing regions can be correlated with the presence of the elongating form of RNA polymerase II or concentrated in the 3′ end of the gene. Public Library of Science 2013-03-22 /pmc/articles/PMC3606415/ /pubmed/23533622 http://dx.doi.org/10.1371/journal.pone.0059389 Text en © 2013 Witham et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Witham, James
Ouboussad, Lylia
Lefevre, Pascal F.
A NF-κB-Dependent Dual Promoter-Enhancer Initiates the Lipopolysaccharide-Mediated Transcriptional Activation of the Chicken Lysozyme in Macrophages
title A NF-κB-Dependent Dual Promoter-Enhancer Initiates the Lipopolysaccharide-Mediated Transcriptional Activation of the Chicken Lysozyme in Macrophages
title_full A NF-κB-Dependent Dual Promoter-Enhancer Initiates the Lipopolysaccharide-Mediated Transcriptional Activation of the Chicken Lysozyme in Macrophages
title_fullStr A NF-κB-Dependent Dual Promoter-Enhancer Initiates the Lipopolysaccharide-Mediated Transcriptional Activation of the Chicken Lysozyme in Macrophages
title_full_unstemmed A NF-κB-Dependent Dual Promoter-Enhancer Initiates the Lipopolysaccharide-Mediated Transcriptional Activation of the Chicken Lysozyme in Macrophages
title_short A NF-κB-Dependent Dual Promoter-Enhancer Initiates the Lipopolysaccharide-Mediated Transcriptional Activation of the Chicken Lysozyme in Macrophages
title_sort nf-κb-dependent dual promoter-enhancer initiates the lipopolysaccharide-mediated transcriptional activation of the chicken lysozyme in macrophages
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3606415/
https://www.ncbi.nlm.nih.gov/pubmed/23533622
http://dx.doi.org/10.1371/journal.pone.0059389
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