Synergistic activation of inflammatory cytokine genes by interferon-γ-induced chromatin remodeling and toll-like receptor signaling.
Synergistic activation of inflammatory cytokine genes by interferon-γ-induced chromatin remodeling and toll-like receptor signaling.
复制标题
干扰素-γ诱导的染色质重塑和Toll样受体信号传导对炎症细胞因子基因的协同激活。
DOI：
10.1016/j.immuni.2013.08.009
复制
发表时间：
2013-09-19
期刊：
影响因子：
32.4
通讯作者：
Ivashkiv LB
中科院分区：
文献类型：
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作者：
Qiao Y;Giannopoulou EG;Chan CH;Park SH;Gong S;Chen J;Hu X;Elemento O;Ivashkiv LB
通过干扰素-γ（IFN-γ）和Toll样受体（TLR）信号传导的炎性细胞因子基因的协同激活对于先天免疫和炎性疾病发病机制是重要的。TLR信号传导的增强（先前提出的机制）不足以解释人巨噬细胞中细胞因子产生的强协同激活。相反，我们发现IFN-γ诱导转录因子STAT 1、IRF-1的持续占据以及TNF、IL 6和IL 12 B基因座的启动子和增强子处的相关组蛋白乙酰化。这种染色质的引发并不激活转录，但大大增加和延长了TLR 4诱导的转录因子和RNA聚合酶II向基因启动子和增强子的募集。引发使细胞因子转录对Jak抑制剂的抑制敏感。全基因组分析揭示了IFN-γ对调控元件的普遍启动，以及启动子和增强子的协同启动与转录的协同诱导。我们的研究结果提供了一种协同机制，IFN-γ创造了一个引发的染色质环境，以增加TLR诱导的基因转录。
Synergistic activation of inflammatory cytokine genes by interferon-γ (IFN-γ) and Toll-like receptor (TLR) signaling is important for innate immunity and inflammatory disease pathogenesis. Enhancement of TLR signaling, a previously proposed mechanism, is insufficient to explain strong synergistic activation of cytokine production in human macrophages. Rather, we found that IFN-γ induced sustained occupancy of transcription factors STAT1, IRF-1 and associated histone acetylation at promoters and enhancers at the TNF, IL6 and IL12B loci. This priming of chromatin did not activate transcription, but greatly increased and prolonged recruitment of TLR4-induced transcription factors and RNA polymerase II to gene promoters and enhancers. Priming sensitized cytokine transcription to suppression by Jak inhibitors. Genome-wide analysis revealed pervasive priming of regulatory elements by IFN-γ, and linked coordinate priming of promoters and enhancers with synergistic induction of transcription. Our results provide a synergy mechanism whereby IFN-γ creates a primed chromatin environment to augment TLR-induced gene transcription.
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DOI：
10.1073/pnas.1017214108
发表时间：
2011-03-29
影响因子：
11.1
作者：
Jin, Fulai;Li, Yan;Natarajan, Rama
通讯作者：
Natarajan, Rama
影响因子：
30.5
作者：
Hu, XY;Herrero, C;Ivashkiv, LB
通讯作者：
Ivashkiv, LB
影响因子：
64.8
作者：
Foster, Simmie L.;Hargreaves, Diana C.;Medzhitov, Ruslan
通讯作者：
Medzhitov, Ruslan
影响因子：
16
作者：
Heinz S;Benner C;Spann N;Bertolino E;Lin YC;Laslo P;Cheng JX;Murre C;Singh H;Glass CK
通讯作者：
Glass CK
影响因子：
30.5
作者：
通讯作者：
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