Transcription of genes encoding synaptic vesicle proteins in human neural stem cells -: Chromatin accessibility, histone methylation pattern, and the essential role of rest
Transcription of genes encoding synaptic vesicle proteins in human neural stem cells -: Chromatin accessibility, histone methylation pattern, and the essential role of rest
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DOI：
10.1074/jbc.m709388200
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发表时间：
2008-04-04
影响因子：
4.8
通讯作者：
Thiel, Gerald
中科院分区：
文献类型：
--
作者：
Ekici, Myriam;Hohl, Mathias;Thiel, Gerald
人HNSC。100神经干细胞在有丝分裂原撤除后上调GFAP的表达。ERK信号通路的激活阻止了GFAP表达的上调。孵育的细胞与视黄酸在有丝分裂原的情况下，增强基础神经元的分化，伴随着神经元基因表达的上调和下调GFAP和巢蛋白的表达。视黄酸处理改变了编码突触蛋白I、突触体蛋白和突触结合蛋白II、IV和VII的神经元基因的组蛋白密码，使其从转录失活状态（组蛋白3的赖氨酸残基9的甲基化）变为转录活性状态（组蛋白3的赖氨酸残基4的甲基化）。相反，GFAP基因的染色质结构从未受刺激的神经干细胞中的转录活性状态转化为视黄酸刺激的细胞中的转录失活状态。此外，视黄酸处理减少了组蛋白去乙酰化酶-1和REST与神经元基因的结合。组蛋白去乙酰化酶活性的抑制诱导编码突触囊泡蛋白的基因在未受刺激的神经干细胞中的表达。类似地，神经元基因转录增强表达后的突变体的REST含有转录激活结构域。这些数据表明，在未分化的人神经干细胞，编码突触囊泡蛋白的神经元基因是可访问的REST突变体和增强组蛋白乙酰化敏感。
Human HNSC. 100 neural stem cells up-regulate expression of GFAP following withdrawal of mitogens. Activation of the ERK signaling pathway prevented the up-regulation of GFAP expression. Incubation of cells with retinoic acid in the absence of mitogens enhanced basal neuronal differentiation that was accompanied by an up-regulation of neuronal gene expression and a down-regulation of GFAP and nestin expression. Retinoic acid treatment changed the histone code of neuronal genes encoding synapsin I, synaptophysin, and synaptotagmins II, IV, and VII from a transcriptionally inactive ( methylation of lysine residue 9 of histone 3) to a transcriptionally active state ( methylation of lysine residue 4 of histone 3). In contrast, the chromatin structure of the GFAP gene is transformed from a transcriptionally active state in unstimulated neural stem cells to a transcriptionally inactive state in retinoic acid-stimulated cells. Additionally, retinoic acid treatment reduced the binding of histone deacetylase-1 and REST to neuronal genes. The inhibition of histone deacetylase activity induced expression of genes encoding synaptic vesicle proteins in unstimulated neural stem cells. Similarly, neuronal gene transcription was enhanced following expression of a mutant of REST that contained a transcriptional activation domain. These data indicate that in undifferentiated human neural stem cells, neuronal genes encoding synaptic vesicle proteins are accessible for the REST mutant and are sensitive to enhanced histone acetylation.