The transcriptional repressor Hes1 attenuates inflammation by regulating transcription elongation
| Autor: | Manfred Gessler, Fei Ning, Inez Rogatsky, Chanyang Ju, Yingli Shang, Yu Qiao, Maddalena Coppo, Baohong Zhao, Lan Kang, Xiaoyu Hu, Li Yu, Bin Zhang, Teng He |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Chemokine endocrine system Transcription Elongation Genetic Positive Transcriptional Elongation Factor B Chemokine CXCL1 Immunology RNA polymerase II Cell Cycle Proteins Biology Article 03 medical and health sciences Mice 0302 clinical medicine Immunology and Allergy Animals HES1 Cells Cultured Regulation of gene expression Inflammation Mice Knockout Transcription Factor HES-1 Arthritis Macrophages CXCL1 Mice Inbred C57BL 030104 developmental biology Gene Expression Regulation Neutrophil Infiltration embryonic structures Mutation biology.protein Cancer research Phosphorylation RNA Polymerase II 030215 immunology |
| Zdroj: | Nature immunology |
| ISSN: | 1529-2916 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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