KDM2B promotes IL-6 production and inflammatory responses through Brg1-mediated chromatin remodeling

作     者：Qingqing Zhou Yunkai Zhang Bo Wang Wenhui Zhou Yong Bi Wanwan Huai Xi Chen Yihan Chen Zhongmin Liu Xingguang Liu Zhenzhen Zhan 

作者机构：Institute of Heart FailureShanghai East HospitalTongji University School of Medicine200120ShanghaiChina National Key Laboratory of Medical Immunology&Institute of ImmunologySecond Military Medical University200433ShanghaiChina Shanghai Fourth People’s HospitalTongji University School of Medicine200081ShanghaiChina Institute of ImmunologyZhejiang University School of Medicine310058HangzhouChina Key Laboratory of Arrhythmias of the Ministry of Education of ChinaShanghai East HospitalTongji University School of Medicine200120ShanghaiChina 

出 版 物：《Cellular & Molecular Immunology》 (中国免疫学杂志（英文版）)

年 卷 期：2020年第17卷第8期

页      面：834-842页

核心收录：

学科分类：0710[理学-生物学] 1004[医学-公共卫生与预防医学(可授医学、理学学位)] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：We thank X.Sun and M.Jin for technical assistance.This work was supported by the National Natural Science Foundation of China(31570871,81571541,81771695,31770970,and 81770094) Program of Shanghai Chief Scientist of Medical and Health Subject(2018BR16) Shuguang Program sponsored by the Shanghai Education Development Foundation and Shanghai Municipal Education Commission(18SG33). 

主　　题：KDM2B IL-6 Brg1 Chromatin remodeling Inflammation 

摘      要：IL-6 plays important and pleiotropic roles in infection and inflammatory diseases,and its production needs to be tightly regulated.However,the epigenetic mechanism underlying Il6 gene transcription remains to be fully elucidated.Here,we report that lysine-specific demethylase 2b(KDM2B),which demethylates H3K4me3 and H3K36me2,is required in macrophages and dendritic cells for the induction of IL-6 but not TNF-α,IL-1,and IFN-β.Compared to wild-type mice,KDM2B-deficient mice were more resistant to endotoxin shock and colitis,with a less severe inflammatory pathogenesis phenotype and decreased IL-6 production in sera.KDM2B selectively bound the Il6 promoter but did not alter histone demethylation;instead,KDM2B interacted with Brahma-related gene 1(Brg1),the core ATPase subunit of SWI/SNF chromatin remodeling complexes,to facilitate chromatin accessibility of the Il6 promoter.Furthermore,KDM2B directly recruited RNA Polymerase II to further initiate and promote Il6 transcription.Thus,our finding identifies a novel nonclassical function of KDM2B in gene-specific transcription initiation and enhancement of Il6 independent of its demethylase activity and adds new insight into the specific epigenetic modification mechanism of inflammatory immune responses.