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3-aminobenzamide: a novel drug to induce in vivoDNA hypermethylation

机译:3-氨基苯甲酰胺:一种诱导体内DNA高甲基化的新药

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Both DNA methylation and core histone hypoacetylation are associated with gene silencing but only recent experiments allowed the interlocking of these two processes. Through such experiments it was shown that the two processes are united in inducing gene silencing through a “shuttle-system” involving the methyl CpG binding protein (MeCP2). In this scenario, it is not clear whether DNA methylation or histone deacetylation is the leader in inducing down regulation of gene expression. Trichostatin A (TSA), a potent inhibitor of histone deacetylase, is usually used to clarify this point. As far as DNA methylation is concerned, only the 5-azacytidine (5-AzaC), able to induce hypomethylation, has been described until now. The aim of this paper is to suggest the use of 3-aminobenzamide (3- ABA) as a method capable of inducing in vivo DNA hypermethylation, so that new experiments could be performed in both directions to clarify the chronology by which the influence on gene expression takes place and to pinpoint the structure of methylated condensed chromatin.
机译:DNA甲基化和核心组蛋白低乙酰化都与基因沉默有关,但只有最近的实验才允许这两个过程互锁。通过这样的实验表明,这两个过程在通过涉及甲基CpG结合蛋白(MeCP2)的“穿梭系统”诱导基因沉默中是统一的。在这种情况下,尚不清楚DNA甲基化或组蛋白脱乙酰化是否是诱导基因表达下调的领导者。 Trichostatin A(TSA)是一种有效的组蛋白脱乙酰基酶抑制剂,通常用于阐明这一点。就DNA甲基化而言,到目前为止,仅描述了能够诱导低甲基化的5-氮杂胞苷(5-AzaC)。本文的目的是建议使用3-氨基苯甲酰胺(3-ABA)作为能够诱导体内DNA超甲基化的方法,以便可以在两个方向上进行新的实验来阐明对基因影响的时间顺序表达发生并查明甲基化缩合染色质的结构。

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