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[酶促甲基化调控各类生物体基因活性中的调控元件]

[Enzymatic methylation of regulatory elements in controlling the activity of genes from various groups of organisms].

作者信息

Mazin A L

出版信息

Mol Biol (Mosk). 1992 Mar-Apr;26(2):244-63.

PMID:1339947
Abstract

About 1800 sequences of gene promoters, enhancers and other types of regulatory elements (REG) have been statistically analysed for investigation of a role for enzymatic DNA methylation in prokaryotes, yeasts, plants, invertebrates, animal viruses, vertebrates and human. The frequencies and localizations of CG and CNG methylated sites and also the number of CG-->TG+CA transitions in different series of REGs have been studied. It was showed that the pro- and eukaryotic REGs with the exception of yeast and drosophila ones have higher CpG-suppression values than the main genome in the same species. About 40% of all the point substitutions in pro- and eukaryotic REGs were found in the CG and CNG methylated sites, that are "hot spots" for C-->T transitions. More than 30% of all analysed REGs have neither sites CG nor CNG and so they are not capable of methylation in vivo. The methylated sites have not been localized in any specific regions of promoters and other types of REGs nor in the flanking sequences of the same genes. Only part of the homological REG's sequences have CG and CNG methylated sites. Therefore the methylation of cytosine residues in any REGs may be not an obligatory condition for normal regulation of the REG activity in cells. Two main REG's families of different length were unexpectedly found in the study. The length of the first one is 9-12 n. and the second is 17-20 n. The families are about 60-80% of other REGs. The essential deficiency of cytosine residues and also triplets of CGG, CCG, CTG and CAG has been showed in the "sense" chain of the REGs. The chain has some abundance of TTG, CCA and CAA triplets. The REG's chains have a strong asymmetry in purine and pyrimidine contents and also in duplets TG and CA frequencies. It may be the result of different reparation effectivity of G-T pairs produced by 5-meC residues deamination in DNA complementary chains. Therefore cytosine methylation in REGs may strongly destabilize the structure, accelerate its divergence in evolution, and disturb the REGs binding with protein factors regulating activity of the genes. The results showed that a function of DNA enzymatic methylation may be hardly realized through the modification of gene regulatory elements.

摘要

为了研究酶促DNA甲基化在原核生物、酵母、植物、无脊椎动物、动物病毒、脊椎动物和人类中的作用,我们对大约1800个基因启动子、增强子和其他类型调控元件(REG)的序列进行了统计分析。研究了不同系列REG中CG和CNG甲基化位点的频率和定位,以及CG→TG+CA转换的数量。结果表明,除酵母和果蝇的REG外,原核生物和真核生物的REG比同一物种的主要基因组具有更高的CpG抑制值。在原核生物和真核生物的REG中,约40%的点突变发生在CG和CNG甲基化位点,这些位点是C→T转换的“热点”。超过30%的分析REG既没有CG位点也没有CNG位点,因此它们在体内不能发生甲基化。甲基化位点未定位在启动子和其他类型REG的任何特定区域,也未定位在同一基因的侧翼序列中。只有部分同源REG序列具有CG和CNG甲基化位点。因此,任何REG中胞嘧啶残基的甲基化可能不是REG在细胞中正常调控活性的必要条件。在这项研究中意外地发现了两个不同长度的主要REG家族。第一个家族的长度为9-12个核苷酸,第二个家族的长度为17-20个核苷酸。这两个家族约占其他REG的60-80%。在REG的“有义”链中显示出胞嘧啶残基以及CGG、CCG、CTG和CAG三联体的明显缺乏。该链中TTG、CCA和CAA三联体相对丰富。REG链在嘌呤和嘧啶含量以及二联体TG和CA频率方面具有很强的不对称性。这可能是由于DNA互补链中5-甲基胞嘧啶残基脱氨产生的G-T对具有不同的修复效率所致。因此,REG中的胞嘧啶甲基化可能会严重破坏结构,加速其在进化中的分化,并干扰REG与调节基因活性的蛋白质因子的结合。结果表明,DNA酶促甲基化的功能可能很难通过基因调控元件的修饰来实现。

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