Prof. Xiaoyu Hu group reported the transcriptional repressor Hes1 controls inflammatory chemokine expression via preventing transcription elongation
Source：Xiaoyu Hu
2016-09-02
The group of Dr. Xiaoyu Hu at Tsinghua University Institute for Immunology demonstrated the transcriptional repressor Hes1 controls chemokine CXCL1 via an unusual mechanism that prevents transcription elongation. This finding is published in August 2016 issue of Nature Immunology entitled “The transcriptional repressor Hes1 attenuates inflammation by regulating transcription elongation.” This work was led by a former postdoctoral fellow of Dr. Hu, Dr. Yingli Shang, who is currently a Principal Investigator in Shandong Agricultural University in Tai’an, China. Dr. Xiaoyu Hu is the corresponding author of this paper. Co-authors include Ph.D students of Dr. Hu from Tsinghua University and scientists from Weill Cornell Medical College and Academy for Advanced Interdisciplinary Studies, Center for Quantitative Biology at Peking University.
Cytokines and chemokines recruit and activate specialized effector cells to sites of inflammation. However, excessive production of inflammatory mediators leads to immune hyper-activation and tissue damage and contributes to the pathogenesis of inflammatory and autoimmune disorders such as rheumatoid arthritis (RA). Thus, expression of inflammatory mediators must be precisely controlled to avoid inappropriate inflammation and tissue damage. To date, 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.
In this study, Dr. Hu’s group found that the transcriptional repressor Hes1 suppressed production of CXCL1, a chemokine that is crucial for recruiting neutrophils. They further demonstrated that 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. These findings reveal Hes1 as a homeostatic suppressor of inflammatory responses that exerts its suppressive function by regulating transcription elongation.
The paper links: http://www.nature.com/ni/journal/v17/n8/full/ni.3486.html
Dr. Hu is currently Principal Investigator at Tsinghua University Institute for Immunology. She was Assistant Professor of Weill Cornell Medical College in New York City, NY. Dr. Hu’s research mainly focuses on understanding the molecular regulatory mechanisms of macrophage activation and its roles of such regulation in the pathogenesis of inflammatory and autoimmune diseases. Dr. Hu’s work has been funded by agencies including the National Natural Science Foundation of China, Minister of Science and Technology of China, U.S. National Institutes of Health R01, American College of Rheumatology, and Lupus Research Institute and has been reported by news media such as Time Online. She is the recipient of multiple awards including UK Royal Society Newton Advanced Fellowship, 1000 Young Talent Program Award, NSFC Young Investigator Award, Young Women Investigator Award from International Cytokine Society, and Young Scholar Award from Arthritis Foundation.
Cytokines and chemokines recruit and activate specialized effector cells to sites of inflammation. However, excessive production of inflammatory mediators leads to immune hyper-activation and tissue damage and contributes to the pathogenesis of inflammatory and autoimmune disorders such as rheumatoid arthritis (RA). Thus, expression of inflammatory mediators must be precisely controlled to avoid inappropriate inflammation and tissue damage. To date, 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.
In this study, Dr. Hu’s group found that the transcriptional repressor Hes1 suppressed production of CXCL1, a chemokine that is crucial for recruiting neutrophils. They further demonstrated that 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. These findings reveal Hes1 as a homeostatic suppressor of inflammatory responses that exerts its suppressive function by regulating transcription elongation.
The paper links: http://www.nature.com/ni/journal/v17/n8/full/ni.3486.html
Dr. Hu is currently Principal Investigator at Tsinghua University Institute for Immunology. She was Assistant Professor of Weill Cornell Medical College in New York City, NY. Dr. Hu’s research mainly focuses on understanding the molecular regulatory mechanisms of macrophage activation and its roles of such regulation in the pathogenesis of inflammatory and autoimmune diseases. Dr. Hu’s work has been funded by agencies including the National Natural Science Foundation of China, Minister of Science and Technology of China, U.S. National Institutes of Health R01, American College of Rheumatology, and Lupus Research Institute and has been reported by news media such as Time Online. She is the recipient of multiple awards including UK Royal Society Newton Advanced Fellowship, 1000 Young Talent Program Award, NSFC Young Investigator Award, Young Women Investigator Award from International Cytokine Society, and Young Scholar Award from Arthritis Foundation.
