Super enhancer regulation of cytokine-induced ...
Document type :
Article dans une revue scientifique: Article original
PMID :
Permalink :
Title :
Super enhancer regulation of cytokine-induced chemokine production in alcoholic hepatitis.
Author(s) :
Liu, M. [Auteur]
Cao, S. [Auteur]
He, L. [Auteur]
Gao, J. [Auteur]
Arab, J. P. [Auteur]
Cui, H. [Auteur]
Xuan, W. [Auteur]
Gao, Y. [Auteur]
Sehrawat, T. S. [Auteur]
Hamdan, F. H. [Auteur]
Ventura-Cots, M. [Auteur]
Argemi, J. [Auteur]
Pomerantz, W. C. K. [Auteur]
Johnsen, S. A. [Auteur]
Lee, J. H. [Auteur]
Gao, F. [Auteur]
Ordog, T. [Auteur]
Mathurin, Philippe [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Revzin, A. [Auteur]
Bataller, R. [Auteur]
Yan, H. [Auteur]
Shah, V. H. [Auteur]
Cao, S. [Auteur]
He, L. [Auteur]
Gao, J. [Auteur]
Arab, J. P. [Auteur]
Cui, H. [Auteur]
Xuan, W. [Auteur]
Gao, Y. [Auteur]
Sehrawat, T. S. [Auteur]
Hamdan, F. H. [Auteur]
Ventura-Cots, M. [Auteur]
Argemi, J. [Auteur]
Pomerantz, W. C. K. [Auteur]
Johnsen, S. A. [Auteur]
Lee, J. H. [Auteur]
Gao, F. [Auteur]
Ordog, T. [Auteur]
Mathurin, Philippe [Auteur]
Institut de Recherche Translationnelle sur l'Inflammation (INFINITE) - U1286
Revzin, A. [Auteur]
Bataller, R. [Auteur]
Yan, H. [Auteur]
Shah, V. H. [Auteur]
Journal title :
Nature Communications
Abbreviated title :
Nat Commun
Volume number :
12
Pages :
4560
Publication date :
2021-07-30
ISSN :
2041-1723
HAL domain(s) :
Sciences du Vivant [q-bio]
English abstract : [en]
Alcoholic hepatitis (AH) is associated with liver neutrophil infiltration through activated cytokine pathways leading to elevated chemokine expression. Super-enhancers are expansive regulatory elements driving augmented ...
Show more >Alcoholic hepatitis (AH) is associated with liver neutrophil infiltration through activated cytokine pathways leading to elevated chemokine expression. Super-enhancers are expansive regulatory elements driving augmented gene expression. Here, we explore the mechanistic role of super-enhancers linking cytokine TNFα with chemokine amplification in AH. RNA-seq and histone modification ChIP-seq of human liver explants show upregulation of multiple CXCL chemokines in AH. Liver sinusoidal endothelial cells (LSEC) are identified as an important source of CXCL expression in human liver, regulated by TNFα/NF-κB signaling. A super-enhancer is identified for multiple CXCL genes by multiple approaches. dCas9-KRAB-mediated epigenome editing or pharmacologic inhibition of Bromodomain and Extraterminal (BET) proteins, transcriptional regulators vital to super-enhancer function, decreases chemokine expression in vitro and decreases neutrophil infiltration in murine models of AH. Our findings highlight the role of super-enhancer in propagating inflammatory signaling by inducing chemokine expression and the therapeutic potential of BET inhibition in AH treatment.Show less >
Show more >Alcoholic hepatitis (AH) is associated with liver neutrophil infiltration through activated cytokine pathways leading to elevated chemokine expression. Super-enhancers are expansive regulatory elements driving augmented gene expression. Here, we explore the mechanistic role of super-enhancers linking cytokine TNFα with chemokine amplification in AH. RNA-seq and histone modification ChIP-seq of human liver explants show upregulation of multiple CXCL chemokines in AH. Liver sinusoidal endothelial cells (LSEC) are identified as an important source of CXCL expression in human liver, regulated by TNFα/NF-κB signaling. A super-enhancer is identified for multiple CXCL genes by multiple approaches. dCas9-KRAB-mediated epigenome editing or pharmacologic inhibition of Bromodomain and Extraterminal (BET) proteins, transcriptional regulators vital to super-enhancer function, decreases chemokine expression in vitro and decreases neutrophil infiltration in murine models of AH. Our findings highlight the role of super-enhancer in propagating inflammatory signaling by inducing chemokine expression and the therapeutic potential of BET inhibition in AH treatment.Show less >
Language :
Anglais
Peer reviewed article :
Oui
Audience :
Internationale
Popular science :
Non
Administrative institution(s) :
Université de Lille
Inserm
CHU Lille
Inserm
CHU Lille
Submission date :
2024-01-12T06:18:42Z
2024-02-27T12:38:38Z
2024-02-27T12:38:38Z
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