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首页> 外文期刊>Molecular and Cellular Biology >Enhancement of β-Globin Locus Control Region-Mediated Transactivation by Mitogen-Activated Protein Kinases through Stochastic and Graded Mechanisms
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Enhancement of β-Globin Locus Control Region-Mediated Transactivation by Mitogen-Activated Protein Kinases through Stochastic and Graded Mechanisms

机译：丝裂素活化的蛋白激酶通过随机和分级机制增强β-球蛋白基因座控制区介导的反式激活。

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Activation of the mitogen-activated protein kinase (MAPK) pathway enhances long-range transactivation by the β-globin locus control region (LCR) (W. K. Versaw, V. Blank, N. M. Andrews, and E. H. Bresnick, Proc. Natl. Acad. Sci. USA 95:8756–8760, 1998). The enhancement requires tandem recognition sites for the hematopoietic transcription factor NF-E2 within the hypersensitive site 2 (HS2) subregion of the LCR. To distinguish between mechanisms of induction involving the activation of silent promoters or the increased efficacy of active promoters, we analyzed basal and MAPK-stimulated HS2 enhancer activity in single, living cells. K562 erythroleukemia cells stably transfected with constructs containing the human Aγ-globin promoter linked to an enhanced green fluorescent protein (EGFP) reporter, with or without HS2, were analyzed for EGFP expression by flow cytometry. When most cells in a population expressed EGFP, MAPK augmented the activity of active promoters. However, under conditions of silencing, in which cells reverted to a state with no measurable EGFP expression, MAPK activated silent promoters. Furthermore, studies of populations of EGFP-expressing and non-EGFP-expressing cells isolated by flow cytometry showed that MAPK activation converted nonexpressing cells into expressing cells and increased expression in expressing cells. These results support a model in which MAPK elicits both graded and stochastic responses to increase HS2-mediated transactivation from single chromatin templates.
机译：丝裂原激活的蛋白激酶（MAPK）途径的激活增强了β球蛋白基因座控制区（LCR）的远程反式激活（WK Versaw，V.Blank，NM Andrews，和EH Bresnick，Proc.Natl.Acad.Sci。美国95：8756-8760，1998）。增强需要LCR的超敏位点2（HS2）子区域内的造血转录因子NF-E2的串联识别位点。为了区分涉及沉默启动子激活或激活启动子功效增强的诱导机制，我们分析了单个活细胞中基础和MAPK刺激的HS2增强子活性。通过流式细胞术分析了用含有连接至增强型绿色荧光蛋白（EGFP）报告基因的人Aγ-球蛋白启动子的构建体稳定转染的K562红白血病细胞的表达，无论是否存在HS2。当群体中的大多数细胞表达EGFP时，MAPK增强了活性启动子的活性。但是，在沉默的情况下，其中细胞恢复到没有可测量的EGFP表达的状态，MAPK激活了沉默启动子。此外，对通过流式细胞术分离的表达EGFP和非EGFP的细胞群体的研究表明，MAPK激活将非表达细胞转化为表达细胞，并增加了表达细胞的表达。这些结果支持了一个模型，其中MAPK引发分级反应和随机反应，以增加单个染色质模板的HS2介导的反式激活。

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