Kaslow D C, Migeon B R
Proc Natl Acad Sci U S A. 1987 Sep;84(17):6210-4. doi: 10.1073/pnas.84.17.6210.
In marsupials and eutherian mammals, X chromosome dosage compensation is achieved by inactivating one X chromosome in female cells; however, in marsupials, the inactive X chromosomes is always paternal, and some genes on the chromosome are partially expressed. To define the role of DNA methylation in maintenance of X chromosome inactivity, we examined loci for glucose-6-phosphate dehydrogenase and hypoxanthine phosphoribosyltransferase in a North American marsupial, the opossum Didelphis virginiana, by using genomic hybridization probes cloned from this species. We find that these marsupial genes are like their eutherian counterparts, with respect to sex differences in methylation of nuclease-insensitive (nonregulatory) chromatin. However, with respect to methylation of the nuclease-hypersensitive (regulatory) chromatin of the glucose-6-phosphate dehydrogenase locus, the opossum gene differs from those of eutherians, as the 5' cluster of CpG dinucleotides is hypomethylated in the paternal as well as the maternal gene. Despite hypomethylation of the 5' CpG cluster, the paternal allele, identified by an enzyme variant, is at best partially expressed; therefore, factors other than methylation are responsible for repression. In light of these results, it seems that the role of DNA methylation in eutherian X dosage compensation is to "lock in" the process initiated by such factors. Because of similarities between dosage compensation in marsupials and trophectoderm derivatives of eutherians, we propose that differences in timing of developmental events--rather than differences in the basic mechanisms of X inactivation--account for features of dosage compensation that differ among mammals.
在有袋类动物和真兽类哺乳动物中，X染色体剂量补偿是通过使雌性细胞中的一条X染色体失活来实现的；然而，在有袋类动物中，失活的X染色体总是父源的，并且该染色体上的一些基因会部分表达。为了确定DNA甲基化在维持X染色体失活中的作用，我们使用从北美有袋类动物弗吉尼亚负鼠（Didelphis virginiana）克隆的基因组杂交探针，检测了葡萄糖-6-磷酸脱氢酶和次黄嘌呤磷酸核糖基转移酶的基因座。我们发现，就核酸酶不敏感（非调节性）染色质的甲基化性别差异而言，这些有袋类动物基因与其真兽类对应基因相似。然而，就葡萄糖-6-磷酸脱氢酶基因座的核酸酶超敏感（调节性）染色质的甲基化而言，负鼠基因与真兽类动物的不同，因为CpG二核苷酸的5'簇在父源基因和母源基因中均为低甲基化。尽管5' CpG簇存在低甲基化，但由一种酶变体鉴定的父源等位基因充其量只是部分表达；因此，甲基化以外的因素负责基因抑制。鉴于这些结果，似乎DNA甲基化在真兽类X染色体剂量补偿中的作用是“锁定”由这些因素启动的过程。由于有袋类动物的剂量补偿与真兽类动物滋养外胚层衍生物之间存在相似性，我们提出发育事件时间的差异——而非X染色体失活基本机制的差异——解释了哺乳动物之间剂量补偿特征的不同。
