Bird A P, Taggart M H, Nicholls R D, Higgs D R
EMBO J. 1987 Apr;6(4):999-1004. doi: 10.1002/j.1460-2075.1987.tb04851.x.
We have analysed CpG frequency and CpG methylation across part of the human alpha-globin locus. Clusters of CpG at the alpha 1 and alpha 2 genes resemble the 'HpaII tiny fragment (HTF) islands' that are characteristic of mammalian 'housekeeping' genes: CpG frequency is not suppressed; testable CpGs are not methylated in DNA from erythroid or nonerythroid tissues, although flanking CpGs are methylated; CpG clusters are approximately 1.5 kb long and extend both upstream and downstream of the alpha-globin transcription start site. These features are not found at genes of the beta-globin locus. The alpha-globin pseudogene (psi alpha 1) is highly homologous to the alpha 2 and alpha 1 genes, but it lacks an HTF island. Sequence comparison shows that a high proportion of CpGs in the alpha 2 gene are substituted by TpG or CpA in the pseudogene. This strongly suggests that an ancestral HTF island at the pseudogene became methylated in the germline, and was lost due to the mutability of 5-methylcytosine.
我们分析了人类α-珠蛋白基因座部分区域的CpG频率和CpG甲基化情况。α1和α2基因处的CpG簇类似于哺乳动物“管家”基因所特有的“HpaII微小片段（HTF）岛”：CpG频率未受抑制；可检测的CpG在红细胞或非红细胞组织的DNA中未发生甲基化，尽管侧翼CpG发生了甲基化；CpG簇约1.5 kb长，在α-珠蛋白转录起始位点的上下游均有延伸。β-珠蛋白基因座的基因未发现这些特征。α-珠蛋白假基因（ψα1）与α2和α1基因高度同源，但它缺乏一个HTF岛。序列比较表明，假基因中α2基因的大部分CpG被TpG或CpA取代。这强烈表明，假基因处的一个祖先HTF岛在种系中发生了甲基化，并由于5-甲基胞嘧啶的可变性而丢失。
