Two-step binding of transcription factors causes sequential chromatin structural changes at the activated IL-2 promoter.

Two-step binding of transcription factors causes sequential chromatin structural changes at the activated IL-2 promoter.
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DOI:
10.4049/jimmunol.1003173
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发表时间:
2011-09-15
期刊:
Journal of immunology (Baltimore, Md. : 1950)
影响因子:
--
通讯作者:
Schwartz RH
Schwartz RH
中科院分区:
其他
文献类型:
--
作者:
Ishihara S;Schwartz RH

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大多数基因启动子对许多转录因子具有多个结合序列,但每种转录因子对染色质重塑的贡献尚不清楚。虽然我们之前发现在T细胞激活过程中,Il2启动子上核小体阵列的排列发生了动态变化,但其时间早于启动子上核小体占用的减少。在这里,我们发现初始核小体重排与NFAT1和AP-1的结合暂时相关(Fos/Jun),而第二步与其他转录因子和RNA聚合酶II的募集并行发生。激活NFAT1或诱导Fos的药理学抑制剂阻断了序列变化的初始阶段。然而,c-Jun磷酸化的抑制并未影响这一步骤,而是阻断了晚期转录因子的结合、creb结合蛋白(CBP)的募集和组蛋白H3在赖氨酸27 (H3K27ac)的乙酰化。因此,转录因子的顺序募集似乎促进了Il2位点染色质重塑的两个独立步骤。
Most gene promoters have multiple binding sequences for many transcription factors, but the contribution of each of these factors to chromatin remodeling is still unclear. Although we previously found a dynamic change in the arrangement of nucleosome arrays at the Il2 promoter during T cell activation, its timing preceded that of a decrease in nucleosome occupancy at the promoter. Here we show that the initial nucleosome rearrangement was temporally correlated with the binding of NFAT1 and AP-1 (Fos/Jun), while the second step occurred in parallel with the recruitment of other transcription factors and RNA polymerase II. Pharmacologic inhibitors for activation of NFAT1 or induction of Fos blocked the initial phase in the sequential changes. This step was not affected, however, by inhibition of c-Jun phosphorylation, which instead blocked the binding of the late transcription factors, the recruitment of CREB-binding protein (CBP) and the acetylation of histone H3 at lysine 27 (H3K27ac). Thus, the sequential recruitment of transcription factors appears to facilitate two separate steps in chromatin remodeling at the Il2 locus.
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