MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response

Abstract Macrophage-dependent inflammatory response is considered a pivotal biological process that contributes to a host of diseases when aberrantly activated. The underlying epigenetic mechanism is not completely understood. We report here that MKL1 was both sufficient and necessary for p65-depend...

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Autores principales:	Liming Yu, Fei Fang, Xin Dai, Huihui Xu, Xiaohong Qi, Mingming Fang, Yong Xu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/0ccf8ea4a734425c983d8fa5f0472379
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spelling	oai:doaj.org-article:0ccf8ea4a734425c983d8fa5f04723792021-12-02T11:40:42ZMKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response10.1038/s41598-017-00301-w2045-2322https://doaj.org/article/0ccf8ea4a734425c983d8fa5f04723792017-03-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00301-whttps://doaj.org/toc/2045-2322Abstract Macrophage-dependent inflammatory response is considered a pivotal biological process that contributes to a host of diseases when aberrantly activated. The underlying epigenetic mechanism is not completely understood. We report here that MKL1 was both sufficient and necessary for p65-dependent pro-inflammatory transcriptional program in immortalized macrophages, in primary human and mouse macrophages, and in an animal model of systemic inflammation (endotoxic shock). Extensive chromatin immunoprecipitation (ChIP) profiling and ChIP-seq analyses revealed that MKL1 deficiency erased key histone modifications synonymous with transactivation on p65 target promoters. Specifically, MKL1 defined histone H3K4 trimethylation landscape for NF-κB dependent transcription. MKL1 recruited an H3K4 trimethyltransferase SET1 to the promoter regions of p65 target genes. There, our work has identified a novel modifier of p65-dependent pro-inflammatory transcription, which may serve as potential therapeutic targets in treating inflammation related diseases.Liming YuFei FangXin DaiHuihui XuXiaohong QiMingming FangYong XuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Liming Yu Fei Fang Xin Dai Huihui Xu Xiaohong Qi Mingming Fang Yong Xu MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response
description	Abstract Macrophage-dependent inflammatory response is considered a pivotal biological process that contributes to a host of diseases when aberrantly activated. The underlying epigenetic mechanism is not completely understood. We report here that MKL1 was both sufficient and necessary for p65-dependent pro-inflammatory transcriptional program in immortalized macrophages, in primary human and mouse macrophages, and in an animal model of systemic inflammation (endotoxic shock). Extensive chromatin immunoprecipitation (ChIP) profiling and ChIP-seq analyses revealed that MKL1 deficiency erased key histone modifications synonymous with transactivation on p65 target promoters. Specifically, MKL1 defined histone H3K4 trimethylation landscape for NF-κB dependent transcription. MKL1 recruited an H3K4 trimethyltransferase SET1 to the promoter regions of p65 target genes. There, our work has identified a novel modifier of p65-dependent pro-inflammatory transcription, which may serve as potential therapeutic targets in treating inflammation related diseases.
format	article
author	Liming Yu Fei Fang Xin Dai Huihui Xu Xiaohong Qi Mingming Fang Yong Xu
author_facet	Liming Yu Fei Fang Xin Dai Huihui Xu Xiaohong Qi Mingming Fang Yong Xu
author_sort	Liming Yu
title	MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response
title_short	MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response
title_full	MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response
title_fullStr	MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response
title_full_unstemmed	MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response
title_sort	mkl1 defines the h3k4me3 landscape for nf-κb dependent inflammatory response
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/0ccf8ea4a734425c983d8fa5f0472379
work_keys_str_mv	AT limingyu mkl1definestheh3k4me3landscapefornfkbdependentinflammatoryresponse AT feifang mkl1definestheh3k4me3landscapefornfkbdependentinflammatoryresponse AT xindai mkl1definestheh3k4me3landscapefornfkbdependentinflammatoryresponse AT huihuixu mkl1definestheh3k4me3landscapefornfkbdependentinflammatoryresponse AT xiaohongqi mkl1definestheh3k4me3landscapefornfkbdependentinflammatoryresponse AT mingmingfang mkl1definestheh3k4me3landscapefornfkbdependentinflammatoryresponse AT yongxu mkl1definestheh3k4me3landscapefornfkbdependentinflammatoryresponse
_version_	1718395561397190656

MKL1 defines the H3K4Me3 landscape for NF-κB dependent inflammatory response

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