期刊
NATURE IMMUNOLOGY
卷 17, 期 8, 页码 930-+出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/ni.3486
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资金
- Ministry of Science and Technology of China [2015CB943201]
- National Natural Science Foundation of China [81422019]
- Tsinghua-Peking Center for Life Sciences
- Institute for Immunology at Tsinghua University
- David Rosensweig HSS Genomics Center
- Rheumatology Research Foundation
- US Department of Defense
- US National Institutes of Health
- Academy of Medical Sciences (AMS) [NAF003\\1001] Funding Source: researchfish
Most of the known regulatory mechanisms that curb inflammatory gene expression target pre-transcription-initiation steps, and evidence for post-initiation regulation of inflammatory gene expression remains scarce. We found that the transcriptional repressor Hes1 suppressed production of CXCL1, a chemokine that is crucial for recruiting neutrophils. Hes1 negatively regulated neutrophil recruitment in vivo in a manner that was dependent on macrophage-produced CXCL1, and it attenuated the severity of inflammatory arthritis. Mechanistically, inhibition of Cxcl1 expression by Hes1 did not involve modification of transcription initiation. Instead, Hes1 inhibited signal-induced recruitment of the positive transcription-elongation complex P-TEFb and thereby prevented phosphorylation of RNA polymerase II at Ser2 and productive elongation. Thus, our results identify Hes1 as a homeostatic suppressor of inflammatory responses that exerts its suppressive function by regulating transcription elongation.
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