MKL1 mediates TNF-α induced pro-inflammatory transcription by bridging the crosstalk between BRG1 and WDR5
Wenping Xu
Quanyi Zhao
Min Wu
Mingrning Fang
Yong Xu
摘要：Tumor necrosis factor alpha (TNF-α) is a cytokine that can potently stimulate the synthesis of a range of proinflammatory mediators in macrophages.The underlying epigenetic mechanism,however,is underexplored.Here we report that the transcriptional modulator megakaryocytic leukemia 1 (MKL1) is associated with a histone H3K4 methyltransferase activity.Re-ChIP assay suggests that MKL 1 interacts with and recruits WDR5,a component of the COMPASS complex responsible for H3K4 methylation,to the promoter regions of pro-inflammatory genes in macrophages treated with TNF-α.WDR5 enhances the ability of MKL1 to stimulate the promoter activities of pro-inflammatory genes.In contrast,silencing of WDR5 attenuates TNF-α induced production of pro-inflammatory mediators and erases the H3K4 methylation from the gene promoters.Of interest,the chromatin remodeling protein BRG1 also plays an essential role in maintaining H3K4 methylation on MKL1 target promoters by interacting with WDR5.MKL1 knockdown disrupts the interaction between BRG1 and WDR5.Together,our data illustrate a role for MKL1 in moderating the crosstalk between BRG1 and WDR5 to activate TNF-α induced pro-inflammatory transcription in macrophages.
机标关键词：
分类号：R329.2(人体形态学)
资助基金：This work was support,in part,by the National Natural Science Foundation of China (81570420)
论文发表日期：2019-01-01
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：9( 164-172 )
英文信息