A2b adenosine signaling represses CIITA transcription via an epigenetic mechanism in vascular smooth muscle cells

Biochimica Et Biophysica Acta
Jun XiaYong Xu

Abstract

Chronic inflammation plays a major role in the pathogenesis of atherosclerosis. Vascular smooth muscle cells (VSMC), by expressing and presenting major histocompatibility complex II (MHC II) molecules, help recruit T lymphocyte and initiate the inflammatory response within the vasculature. We have previously shown that VSMCs isolated from mice with deficient adenosine A2b receptor (A2b-null) exhibit higher expression of class II transactivator (CIITA), the master regulator of MHC II transcription, compared to wild type littermates. Here we report that activation of A2b adenosine signaling suppresses CIITA expression in human aortic smooth muscle cells. Down-regulation of CIITA expression was largely attributable to transcriptional repression of type III and IV promoters. Chromatin immunoprecipitation (ChIP) analyses revealed that A2b signaling repressed CIITA transcription by attenuating specific histone modifications on the CIITA promoters in a STAT1-dependent manner. STAT1 interacted with PCAF/GCN5, histone H3K9 acetyltransferases, and WDR5, a key component of the mammalian H3K4 methyltransferase complex, to activate CIITA transcription. A2b signaling prevented recruitment of PCAF/GCN5 and WDR5 to the CIITA promoters in a STA...Continue Reading

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Citations

Aug 5, 2015·Biochimica Et Biophysica Acta·Zhiwen FanYong Xu
Mar 15, 2016·Biochimica Et Biophysica Acta·Zhiwen FanYong Xu
Oct 22, 2016·Biochimica Et Biophysica Acta·Sheng ZengYong Xu
Oct 13, 2016·Life Sciences·Cesar SepúlvedaEduardo Fuentes
Feb 9, 2017·Immunology and Cell Biology·David AllardJohn Stagg
Jun 1, 2018·Physiological Reviews·Pier Andrea BoreaKatia Varani
Jul 25, 2019·Current Pharmaceutical Design·Bapi GorainSubrat Kumar Bhattamisra
Apr 27, 2016·Current Opinion in Clinical Nutrition and Metabolic Care·Dashzeveg Bayarsaihan
Jun 15, 2018·Molecular Medicine Reports·Wanlin JiangChandra S Boosani
Oct 20, 2019·International Journal of Molecular Sciences·Zhan-Guo Gao, Kenneth A Jacobson

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