Document Detail

MRTF-A mediates LPS-induced pro-inflammatory transcription by interacting with the COMPASS complex.
MedLine Citation:
PMID:  25189621     Owner:  NLM     Status:  Publisher    
Chronic inflammation underscores the pathogenesis of a range of human diseases. Lipopolysaccharide (LPS) elicits strong pro-inflammatory response in macrophages via the transcription factor NF-κB. The epigenetic mechanism underlying LPS-induced pro-inflammatory transcription is not completely appreciated. Herein we describe a role for myocardin related transcription factor A, or MRTF-A, in this process. MRTF-A over-expression potentiated while MRTF-A silencing dampened NF-κB dependent pro-inflammatory transcription. MRTF-A deficiency also alleviated the synthesis of pro-inflammatory mediators in a mouse model of colitis. LPS promoted the recruitment of MRTF-A to the promoters of pro-inflammatory genes in a NF-κB dependent manner. Reciprocally, MRTF-A influenced the nuclear enrichment and target binding of NF-κB. Mechanistically, MRTF-A was necessary for the accumulation of active histone modifications on NF-κB target promoters by communicating with the histone H3K4 methyltransferase complex (COMPASS). Silencing of individual members of COMPASS, including ASH2, WDR5, and SET1, down-regulated the production of pro-inflammatory mediators and impaired the NF-κB kinetics. In summary, our work has uncovered a previously unknown function for MRTF-A and provided insights into the rationalized development of anti-inflammatory therapeutic strategies.
Liming Yu; Xinyu Weng; Peng Liang; Xin Dai; Xiaoyan Wu; Huihui Xu; Mingming Fang; Fei Fang; Yong Xu
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2014-9-4
Journal Detail:
Title:  Journal of cell science     Volume:  -     ISSN:  1477-9137     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2014 Sep 
Date Detail:
Created Date:  2014-9-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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