Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
Genominformatik, Institut für Humangenetik, Medizinische Fakultät, Universität Duisburg-Essen, Essen, Germany.
Genome Biol Evol. 2014 Jun 12;6(7):1579-88. doi: 10.1093/gbe/evu125.
Imprinting of the human RB1 gene is due to the presence of a differentially methylated CpG island (CGI) in intron 2, which is part of a retrocopy derived from the PPP1R26 gene on chromosome 9. The murine Rb1 gene does not have this retrocopy and is not imprinted. We have investigated whether the RB1/Rb1 locus is unique with respect to these differences. For this, we have compared the CGIs from human and mouse by in silico analyses. We have found that the human genome does not only contain more CGIs than the mouse, but the proportion of intronic CGIs is also higher (7.7% vs. 3.5%). At least 2,033 human intronic CGIs are not present in the mouse. Among these CGIs, 104 show sequence similarities elsewhere in the human genome, which suggests that they arose from retrotransposition. We could narrow down the time points when most of these CGIs appeared during evolution. Their methylation status was analyzed in two monocyte methylome data sets from whole-genome bisulfite sequencing and in 18 published methylomes. Four CGIs, which are located in the RB1, ASRGL1, PARP11, and PDXDC1 genes, occur as methylated and unmethylated copies. In contrast to imprinted methylation at the RB1 locus, differential methylation of the ASRGL1 and PDXDC1 CGIs appears to be sequence dependent. Our study supports the notion that the epigenetic fate of the retrotransposed DNA depends on its sequence and selective forces at the integration site.
人类 RB1 基因的印迹是由于其内含子 2 中存在一个差异甲基化 CpG 岛（CGI），该 CGI 是来自 9 号染色体 PPP1R26 基因的反转录副本的一部分。鼠类的 Rb1 基因没有这个反转录副本，也没有印迹。我们研究了 RB1/Rb1 基因座在这些差异方面是否是独特的。为此，我们通过计算机分析比较了人类和小鼠的 CGI。我们发现，与小鼠相比，人类基因组不仅含有更多的 CGI，而且内含子 CGI 的比例也更高（7.7%对 3.5%）。至少有 2033 个人类内含子 CGI 不存在于小鼠中。在这些 CGI 中，有 104 个在人类基因组的其他地方显示出序列相似性，这表明它们是通过反转录转座产生的。我们可以缩小这些 CGI 大部分在进化过程中出现的时间点。我们在来自全基因组亚硫酸氢盐测序的两个单核细胞甲基组数据集和 18 个已发表的甲基组中分析了它们的甲基化状态。四个 CGI，位于 RB1、ASRGL1、PARP11 和 PDXDC1 基因中，作为甲基化和非甲基化拷贝存在。与 RB1 基因座的印迹甲基化相反，ASRGL1 和 PDXDC1 CGI 的差异甲基化似乎依赖于序列。我们的研究支持这样一种观点，即反转录 DNA 的表观遗传命运取决于其序列和整合位点的选择压力。
