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Sci Rep. 2017 Mar 15;7(1):191. doi: 10.1038/s41598-017-00301-w.

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

Yu L1, Fang F1, Dai X1, Xu H1, Qi X1, Fang M2, Xu Y3,4.

Author information

1
Key Laboratory of Cardiovascular Disease and Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Pathophysiology, Nanjing Medical University, Nanjing, China.
2
Key Laboratory of Cardiovascular Disease and Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Pathophysiology, Nanjing Medical University, Nanjing, China. dafeifang@163.com.
3
Key Laboratory of Cardiovascular Disease and Key Laboratory of Human Functional Genomics of Jiangsu Province, Department of Pathophysiology, Nanjing Medical University, Nanjing, China. yxu2005@gmail.com.
4
State Key Laboratory of Nature Medicines, China Pharmaceutical University, Nanjing, China. yxu2005@gmail.com.

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.

PMID:
28298643
PMCID:
PMC5428227
DOI:
10.1038/s41598-017-00301-w
[Indexed for MEDLINE]
Free PMC Article

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