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The transcriptional repressor Hes1 attenuates inflammation via regulating transcriptional elongation

Most of the known regulatory mechanisms that curb inflammatory gene expression target pre-transcription initiation steps and evidence for regulation of inflammatory gene expression post initiation remains scarce. Here we show that transcription repressor hairy and enhancer of split 1 (Hes1) suppress...

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Autores principales: Shang, Yingli, Coppo, Maddalena, He, Teng, Ning, Fei, Yu, Li, Kang, Lan, Zhang, Bin, Ju, Chanyang, Qiao, Yu, Zhao, Baohong, Gessler, Manfred, Rogatsky, Inez, Hu, Xiaoyu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955730/
https://www.ncbi.nlm.nih.gov/pubmed/27322654
http://dx.doi.org/10.1038/ni.3486
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author Shang, Yingli
Coppo, Maddalena
He, Teng
Ning, Fei
Yu, Li
Kang, Lan
Zhang, Bin
Ju, Chanyang
Qiao, Yu
Zhao, Baohong
Gessler, Manfred
Rogatsky, Inez
Hu, Xiaoyu
author_facet Shang, Yingli
Coppo, Maddalena
He, Teng
Ning, Fei
Yu, Li
Kang, Lan
Zhang, Bin
Ju, Chanyang
Qiao, Yu
Zhao, Baohong
Gessler, Manfred
Rogatsky, Inez
Hu, Xiaoyu
author_sort Shang, Yingli
collection PubMed
description Most of the known regulatory mechanisms that curb inflammatory gene expression target pre-transcription initiation steps and evidence for regulation of inflammatory gene expression post initiation remains scarce. Here we show that transcription repressor hairy and enhancer of split 1 (Hes1) suppresses production of CXCL1, a chemokine crucial for recruiting neutrophils. Hes1 negatively regulates neutrophil recruitment in vivo in a manner that is dependent on macrophage-produced CXCL1 and attenuates severity of inflammatory arthritis. Mechanistically, inhibition of Cxcl1 expression by Hes1 does not involve modification of transcription initiation. Instead, Hes1 inhibits signal-induced recruitment of positive transcription elongation complex P-TEFb, thereby preventing phosphorylation of RNA polymerase II on serine-2 and productive elongation. Thus, our results identify Hes1 as a homeostatic suppressor of inflammatory responses which exerts its suppressive function by regulating transcription elongation.
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spelling pubmed-49557302016-12-20 The transcriptional repressor Hes1 attenuates inflammation via regulating transcriptional elongation Shang, Yingli Coppo, Maddalena He, Teng Ning, Fei Yu, Li Kang, Lan Zhang, Bin Ju, Chanyang Qiao, Yu Zhao, Baohong Gessler, Manfred Rogatsky, Inez Hu, Xiaoyu Nat Immunol Article Most of the known regulatory mechanisms that curb inflammatory gene expression target pre-transcription initiation steps and evidence for regulation of inflammatory gene expression post initiation remains scarce. Here we show that transcription repressor hairy and enhancer of split 1 (Hes1) suppresses production of CXCL1, a chemokine crucial for recruiting neutrophils. Hes1 negatively regulates neutrophil recruitment in vivo in a manner that is dependent on macrophage-produced CXCL1 and attenuates severity of inflammatory arthritis. Mechanistically, inhibition of Cxcl1 expression by Hes1 does not involve modification of transcription initiation. Instead, Hes1 inhibits signal-induced recruitment of positive transcription elongation complex P-TEFb, thereby preventing phosphorylation of RNA polymerase II on serine-2 and productive elongation. Thus, our results identify Hes1 as a homeostatic suppressor of inflammatory responses which exerts its suppressive function by regulating transcription elongation. 2016-06-20 2016-08 /pmc/articles/PMC4955730/ /pubmed/27322654 http://dx.doi.org/10.1038/ni.3486 Text en Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Shang, Yingli
Coppo, Maddalena
He, Teng
Ning, Fei
Yu, Li
Kang, Lan
Zhang, Bin
Ju, Chanyang
Qiao, Yu
Zhao, Baohong
Gessler, Manfred
Rogatsky, Inez
Hu, Xiaoyu
The transcriptional repressor Hes1 attenuates inflammation via regulating transcriptional elongation
title The transcriptional repressor Hes1 attenuates inflammation via regulating transcriptional elongation
title_full The transcriptional repressor Hes1 attenuates inflammation via regulating transcriptional elongation
title_fullStr The transcriptional repressor Hes1 attenuates inflammation via regulating transcriptional elongation
title_full_unstemmed The transcriptional repressor Hes1 attenuates inflammation via regulating transcriptional elongation
title_short The transcriptional repressor Hes1 attenuates inflammation via regulating transcriptional elongation
title_sort transcriptional repressor hes1 attenuates inflammation via regulating transcriptional elongation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4955730/
https://www.ncbi.nlm.nih.gov/pubmed/27322654
http://dx.doi.org/10.1038/ni.3486
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