USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation
Abstract Chromatin modifications, such as histone acetylation, ubiquitination, and methylation, play fundamental roles in maintaining chromatin architecture and regulating gene transcription. Although their crosstalk in chromatin remodeling has been gradually uncovered, the functional relationship b...
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doaj-069fec4c3976414c8dd248e383286b0f2020-11-25T04:06:19ZengWileyAdvanced Science2198-38442020-11-01722n/an/a10.1002/advs.202002680USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve InflammationZhiyao Zhao0Zexiong Su1Puping Liang2Di Liu3Shuai Yang4Yaoxing Wu5Ling Ma6Junyan Feng7Xiya Zhang8Chenglei Wu9Junjiu Huang10Jun Cui11MOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaMOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaMOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaMOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaMOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaMOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaMOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaMOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaMOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaMOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaMOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaMOE Key Laboratory of Gene Function and Regulation State Key Laboratory of Biocontrol School of Life Sciences Sun Yat‐sen University Guangzhou Guangdong 510006 ChinaAbstract Chromatin modifications, such as histone acetylation, ubiquitination, and methylation, play fundamental roles in maintaining chromatin architecture and regulating gene transcription. Although their crosstalk in chromatin remodeling has been gradually uncovered, the functional relationship between histone ubiquitination and methylation in regulating immunity and inflammation remains unclear. Here, it is reported that USP38 is a novel histone deubiquitinase that works together with the histone H3K4 modifier KDM5B to orchestrate inflammatory responses. USP38 specifically removes the monoubiquitin on H2B at lysine 120, which functions as a prerequisite for the subsequent recruitment of demethylase KDM5B to the promoters of proinflammatory cytokines Il6 and Il23a during LPS stimulation. KDM5B in turn inhibits the binding of NF‐κB transcription factors to the Il6 and Il23a promoters by reducing H3K4 trimethylation. Furthermore, USP38 can bind to KDM5B and prevent it from proteasomal degradation, which further enhances the function of KDM5B in the regulation of inflammation‐related genes. Loss of Usp38 in mice markedly enhances susceptibility to endotoxin shock and acute colitis, and these mice display a more severe inflammatory phenotype compared to wild‐type mice. The studies identify USP38‐KDM5B as a distinct chromatin modification complex that restrains inflammatory responses through manipulating the crosstalk of histone ubiquitination and methylation.https://doi.org/10.1002/advs.202002680deubiquitinasehistone modificationinflammationKDM5BubiquitinationUSP38 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Zhiyao Zhao Zexiong Su Puping Liang Di Liu Shuai Yang Yaoxing Wu Ling Ma Junyan Feng Xiya Zhang Chenglei Wu Junjiu Huang Jun Cui |
spellingShingle |
Zhiyao Zhao Zexiong Su Puping Liang Di Liu Shuai Yang Yaoxing Wu Ling Ma Junyan Feng Xiya Zhang Chenglei Wu Junjiu Huang Jun Cui USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation Advanced Science deubiquitinase histone modification inflammation KDM5B ubiquitination USP38 |
author_facet |
Zhiyao Zhao Zexiong Su Puping Liang Di Liu Shuai Yang Yaoxing Wu Ling Ma Junyan Feng Xiya Zhang Chenglei Wu Junjiu Huang Jun Cui |
author_sort |
Zhiyao Zhao |
title |
USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation |
title_short |
USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation |
title_full |
USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation |
title_fullStr |
USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation |
title_full_unstemmed |
USP38 Couples Histone Ubiquitination and Methylation via KDM5B to Resolve Inflammation |
title_sort |
usp38 couples histone ubiquitination and methylation via kdm5b to resolve inflammation |
publisher |
Wiley |
series |
Advanced Science |
issn |
2198-3844 |
publishDate |
2020-11-01 |
description |
Abstract Chromatin modifications, such as histone acetylation, ubiquitination, and methylation, play fundamental roles in maintaining chromatin architecture and regulating gene transcription. Although their crosstalk in chromatin remodeling has been gradually uncovered, the functional relationship between histone ubiquitination and methylation in regulating immunity and inflammation remains unclear. Here, it is reported that USP38 is a novel histone deubiquitinase that works together with the histone H3K4 modifier KDM5B to orchestrate inflammatory responses. USP38 specifically removes the monoubiquitin on H2B at lysine 120, which functions as a prerequisite for the subsequent recruitment of demethylase KDM5B to the promoters of proinflammatory cytokines Il6 and Il23a during LPS stimulation. KDM5B in turn inhibits the binding of NF‐κB transcription factors to the Il6 and Il23a promoters by reducing H3K4 trimethylation. Furthermore, USP38 can bind to KDM5B and prevent it from proteasomal degradation, which further enhances the function of KDM5B in the regulation of inflammation‐related genes. Loss of Usp38 in mice markedly enhances susceptibility to endotoxin shock and acute colitis, and these mice display a more severe inflammatory phenotype compared to wild‐type mice. The studies identify USP38‐KDM5B as a distinct chromatin modification complex that restrains inflammatory responses through manipulating the crosstalk of histone ubiquitination and methylation. |
topic |
deubiquitinase histone modification inflammation KDM5B ubiquitination USP38 |
url |
https://doi.org/10.1002/advs.202002680 |
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