NF-κB directs dynamic super enhancer formation in inflammation and atherogenesis.
NF-κB directs dynamic super enhancer formation in inflammation and atherogenesis.
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DOI：
10.1016/j.molcel.2014.08.024
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发表时间：
2014-10-23
期刊：
影响因子：
16
通讯作者：
Plutzky, Jorge
中科院分区：
文献类型：
--
作者：
Brown, Jonathan D.;Lin, Charles Y.;Duan, Qiong;Griffin, Gabriel;Federation, Alexander J.;Paranal, Ronald M.;Bair, Steven;Newton, Gail;Lichtman, Andrew H.;Kung, Andrew L.;Yang, Tianlun;Wang, Hong;Luscinskas, Francis W.;Croce, Kevin J.;Bradner, James E.;Plutzky, Jorge
Proinflammatory stimuli elicit rapid transcriptional responses via transduced signals to master regulatory transcription factors. To explore the role of chromatin-dependent signal transduction in the atherogenic inflammatory response, we characterized the dynamics, structure and function of regulatory elements in the activated endothelial cell epigenome. Stimulation with tumor necrosis factor alpha prompted a dramatic and rapid global redistribution of chromatin activators to massive de novo clustered enhancer domains. Inflammatory super enhancers formed by NF-κB accumulate at the expense of immediately decommissioned, basal endothelial super enhancers, despite persistent histone hyperacetylation. Mass action of enhancer factor redistribution causes momentous swings in transcriptional initiation and elongation. A chemical genetic approach reveals a requirement for BET bromodomains in communicating enhancer remodeling to RNA polymerase and orchestrating the transition to the inflammatory cell state, demonstrated in activated endothelium and macrophages. BET bromodomain inhibition abrogates super enhancer mediated inflammatory transcription, atherogenic endothelial responses and atherosclerosis in vivo.
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选择性抑制BET溴结构域。
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
64.5
作者：
Matzuk MM;McKeown MR;Filippakopoulos P;Li Q;Ma L;Agno JE;Lemieux ME;Picaud S;Yu RN;Qi J;Knapp S;Bradner JE
通讯作者：
Bradner JE
影响因子：
64.8
作者：
Jin, Fulai;Li, Yan;Dixon, Jesse R.;Selvaraj, Siddarth;Ye, Zhen;Lee, Ah Young;Yen, Chia-An;Schmitt, Anthony D.;Espinoza, Celso A.;Ren, Bing
通讯作者：
Ren, Bing
影响因子：
64.5
作者：
Hnisz D;Abraham BJ;Lee TI;Lau A;Saint-André V;Sigova AA;Hoke HA;Young RA
通讯作者：
Young RA
影响因子：
64.5
作者：
Anand P;Brown JD;Lin CY;Qi J;Zhang R;Artero PC;Alaiti MA;Bullard J;Alazem K;Margulies KB;Cappola TP;Lemieux M;Plutzky J;Bradner JE;Haldar SM
通讯作者：
Haldar SM