Developmental stage dependent regulation of DNA methylation and chromatin modification in a immature astrocyte specific gene promoter
Developmental stage dependent regulation of DNA methylation and chromatin modification in a immature astrocyte specific gene promoter
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DOI：
10.1016/j.febslet.2004.07.029
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发表时间：
2004-08-13
期刊：
影响因子：
3.5
通讯作者：
Taga, T
中科院分区：
文献类型：
--
作者：
Namihira, M;Nakashima, K;Taga, T
星形胶质细胞是大脑发育过程中神经元之后的神经上皮细胞产生的。然而，这种顺序生成的机制尚不完全清楚。在这里，我们发现编码未成熟星形胶质细胞标记物 S100beta 的基因启动子中的特定胞嘧啶残基变得去甲基化，与胚胎 (E)14 天开始表达 S100beta 的时间相关。此外，星形胶质细胞诱导细胞因子 BMP2 会增加 E14 神经上皮细胞 CpG 位点周围的组蛋白乙酰化，但当表达 S100beta 的星形胶质细胞不存在时，E11 则不会增加。此外，与 E11 相比，E14 时神经上皮细胞中甲基 DNA 结合蛋白 MeCP2 与 S1000 基因启动子的结合减少。因此，特定 CpG 位点的去甲基化被认为是调节发育中大脑中星形胶质细胞分化的关键决定因素。 (C) 2004 年欧洲生化学会联合会。由 Elsevier B.V. 出版。保留所有权利。
Astrocytes are generated from neuroepithelial cells after neurons during brain development. However, the mechanism of this sequential generation is not fully understood. Here, we show that a particular cytosine residue in the promoter of the gene encoding the immature astrocyte marker, S100beta, becomes demethylated, correlating with the time when the S100beta expression commences at embryonic day (E)14. In addition, astrocyte-inducing cytokine, BMP2, increased histone acetylation around the CpG site in neuroepithelial cells at E14 but not Ell when S100beta expressing astrocytes are absent. Furthermore, binding of a methyl DNA binding protein, MeCP2, to the S1000 gene promoter in neuroepithelial cells was reduced at E14 compared to E11. Thus, demethylation of specific CpG site is suggested to be a critical determinant in regulating astrocyte differentiation in the developing brain. (C) 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.