Mazin A L, Vaniushin B F
Mol Biol (Mosk). 1987 May-Jun;21(3):678-87.
From nucleotide sequences of more than 70 histones genes in 15 species of eucaryotes the probable frequency was determined for CpG----TpG + CpA substitutions, occurring as a result of deamination of 5-methylcytosine residues in DNA. It was found that histone genes differ in the character of CpG methylation with respect to the species studied and may be divided into three groups differing in the value of CpG suppression. In one of them, M-, CpG dinucleotides must have not been methylated throughout the existence of these genes; in another, M+, nearly every other CpG has undergone transition. In the third group, M +/-, no more than 20% of CpG have steadily undergone methylation (and mutation). The CpG deficiency in M+ and M +/- histone genes is in general proportional to the level of methylation of total DNA in different species. It has been noted that the genes of different core histones in the same organism are characterized, as a rule, by the same type of CpG methylation and belong to the same group. Genes H1 and H5 show a higher level of CpG suppression and thus have a higher degree of methylation than the genes of core histones from the same organism. The most conserved among the histone genes, those for H3 and H4 in particular, must have not been methylated in the majority of the species studied. The distribution of methylated and non-methylated spacers and coding sequences of histone genes of man, mouse, hen and yeast reveals a mosaic pattern. It has been found that 5'-flanked regions in most cases are methylated more than respective genes, while the G + C content in them is significantly lower, compared with the coding gene sequences. The absence of methylation in the 5'-regulatory regions does not appear to be mandatory for histone genes. It has been established that the genes of the same histones may differ in the level of methylation even in more or less closely related species. Group M- comprises genes of core histones of man, hen, sea urchin, Drosophila, Neurospora and wheat; group M +/- includes analogous genes of mouse, Xenopus, trout and sea urchins. The results obtained testify against the possible universal involvement of methylation in the regulation of histone gene expression.
通过测定15种真核生物中70多个组蛋白基因的核苷酸序列,确定了因DNA中5 - 甲基胞嘧啶残基脱氨而发生的CpG→TpG + CpA替换的可能频率。研究发现,在所研究的物种中,组蛋白基因在CpG甲基化特征方面存在差异,可分为CpG抑制值不同的三组。其中一组,M - ,在这些基因存在的整个过程中,CpG二核苷酸肯定未被甲基化;另一组,M + ,几乎每隔一个CpG就发生了转变。在第三组,M + / - ,不超过20%的CpG稳定地发生了甲基化(和突变)。M + 和M + / - 组蛋白基因中CpG的缺乏通常与不同物种中总DNA的甲基化水平成正比。值得注意的是,同一生物体中不同核心组蛋白的基因通常具有相同类型的CpG甲基化,属于同一组。H1和H5基因显示出较高水平的CpG抑制,因此比同一生物体中核心组蛋白的基因具有更高程度的甲基化。在组蛋白基因中最保守的,特别是H3和H4的基因,在大多数所研究的物种中肯定未被甲基化。人类、小鼠、母鸡和酵母的组蛋白基因的甲基化和非甲基化间隔区及编码序列的分布呈现出镶嵌模式。研究发现,在大多数情况下,5'侧翼区的甲基化程度高于相应基因,而其中的G + C含量与编码基因序列相比明显较低。5'调控区不存在甲基化对组蛋白基因来说似乎并非是必需的。已经确定,即使在亲缘关系或多或少相近的物种中,相同组蛋白的基因在甲基化水平上也可能存在差异。M - 组包括人类、母鸡、海胆、果蝇、粗糙脉孢菌和小麦的核心组蛋白基因;M + / - 组包括小鼠、非洲爪蟾、鳟鱼和海胆的类似基因。所得结果证明甲基化不太可能普遍参与组蛋白基因表达的调控。