MeCP2 expression and promoter methylation of cyclin D1 gene are associated with cyclin D1 expression in developing rat epididymal duct.

MeCP2 expression and promoter methylation of cyclin D1 gene are associated with cyclin D1 expression in developing rat epididymal duct.
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Cyclin D1基因的MECP2表达和启动子甲基化与Cyclin d1表达在发育中的大鼠附子导管中有关。

DOI:
10.1267/ahc.08025
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发表时间:
2008-10-29
影响因子:
2.4
通讯作者:
Kitazawa, Sohei
Kitazawa, Sohei
中科院分区:
生物学4区
文献类型:
--
作者:
Darwanto, Agus;Kitazawa, Riko;Mori, Kiyoshi;Kondo, Takeshi;Kitazawa, Sohei

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通过招募甲基-CpG结合蛋白(MeCP)实现基因的高甲基化依赖性沉默。在MeCP中,MeCP 2在各种类型的细胞中表达最丰富和普遍。我们首先筛选了MeCP 2在成年和发育中大鼠组织中的分布和表达模式,发现MeCP 2的强表达,尽管在正常组织、小肠的神经节细胞和肠上皮、大脑中的浦肯野细胞和神经元、精原细胞和睾丸附睾管的上皮细胞中普遍存在。然后,我们评估的表达和甲基化模式的细胞周期蛋白D1的启动子区域的免疫组织化学和亚硫酸氢钠映射,发现细胞周期蛋白D1在附睾管的表达迅速下降,在大鼠发育过程中:强的新生大鼠和非常弱或几乎阴性的7天大的大鼠。7日龄大鼠附睾管中cyclin D1启动子区CpG和非CpG位点的甲基化胞嘧啶多见,而新生大鼠附睾管中未见甲基化胞嘧啶。有趣的是,MeCP 2表达也随着甲基化的增加而增加。附睾管中Cyclin D1的表达可能受到MeCP 2表达和启动子甲基化协同增加的表观遗传机制的有效调控。
Hypermethylation-dependent silencing of the gene is achieved by recruiting methyl-CpG binding proteins (MeCPs). Among the MeCPs, MeCP2 is the most abundantly and ubiquitously expressed in various types of cells. We first screened the distribution and expression pattern of MeCP2 in adult and developing rat tissues and found strong MeCP2 expression, albeit rather ubiquitously among normal tissues, in ganglion cells and intestinal epithelium in the small intestine, in Purkinje cells and neurons in the brain, in spermatogonia and in epithelial cells in the epididymal duct of the testis. We then assessed the expression and the methylation pattern of the promoter region of cyclin D1 by immunohistochemistry and sodium bisulfite mapping, and found that cyclin D1 expression in the epididymal duct decreased rapidly during rat development: strong in newborn rats and very weak or almost negative in 7-day-old rats. Mirroring the decrease of cyclin D1 expression, methylated cytosine at both CpG and non-CpG loci in the cyclin D1 promoter was frequently observed in the epididymal duct of 7-day-old rats but not in that of newborn rats. Interestingly, MeCP2 expression also increased concomitant with the increase of methylation. Cyclin D1 expression in the epididymal duct may be efficiently regulated by the epigenetic mechanism of the cooperative increase of MeCP2 expression and promoter methylation.
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发表时间: 1999-01-01
影响因子: 2.3
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