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MKL 1 is an epigenetic mediator of TNF ‐α‐induced proinflammatory transcription in macrophages by interacting with ASH 2
Author(s) -
Song Mingzi,
Fang Fei,
Dai Xin,
Yu Liming,
Fang Mingming,
Xu Yong
Publication year - 2017
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1002/1873-3468.12601
Subject(s) - proinflammatory cytokine , transactivation , epigenetics , tumor necrosis factor alpha , transcription factor , mediator , biology , microbiology and biotechnology , inflammation , immunology , genetics , gene
Tumor necrosis factor alpha ( TNF ‐α) is a prototypical proinflammatory cytokine that can elicit strong inflammation in macrophages by activating NF ‐κB. The underlying epigenetic mechanism is obscure. We show here that megakaryocytic leukemia 1 (MKL1) is an epigenetic mediator of TNF ‐α‐induced proinflammatory transcription. Overexpression of a dominant negative form of MKL 1 abrogates TNF ‐α‐induced transactivation of proinflammatory genes. Proteomic analysis identifies the histone H3K4 trimethyltransferase ASH 2 as a potential cofactor for MKL 1. In response to TNF ‐α stimulation, ASH 2 is recruited by MKL 1 and interacts with MKL 1 to catalyze H3K4 di‐ and trimethylation. ASH 2 modulates proinflammatory transcription at least in part by altering the affinity of p65 for target promoters. Together, our data support an interplay between MKL 1 and ASH 2 to promote TNF ‐α‐induced proinflammatory transcription in macrophages.