Transcription of genes encoding synaptic vesicle proteins in human neural stem cells -: Chromatin accessibility, histone methylation pattern, and the essential role of rest

被引:31
作者
Ekici, Myriam [1 ]
Hohl, Mathias [1 ]
Schuit, Frans [2 ]
Martinez-Serrano, Alberto [3 ]
Thiel, Gerald [1 ]
机构
[1] Univ Saarland, Med Ctr, Dept Med Biochem & Mol Biol, D-66421 Homburg, Germany
[2] Katholieke Univ Leuven, Dept Mol Cell Biol, B-3000 Louvain, Belgium
[3] UAM, CSIC, Ctr Mol Biol Severo Ochoa, Madrid 28049, Spain
关键词
D O I
10.1074/jbc.M709388200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
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收藏
页码:9257 / 9268
页数:12
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