Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Iceland, IS-101, and Department of Genetics and Molecular Medicine, Landspitali-University Hospital, Reykjavik, IS-101, Iceland.
Gene. 2012 Jan 15;492(1):104-9. doi: 10.1016/j.gene.2011.10.046. Epub 2011 Nov 7.
A potential relationship between transposon-derived repeats (TDR) and human germline methylation is of biological importance since many genes are flanked by TDR and methylation could affect the expression of nearby genes. Furthermore, DNA methylation has been suggested as a global defense mechanism against genome instability threatened by TDR. We studied the correlation between the density of HapMap methyl-associated SNPs (mSNPs), a marker of germline methylation, and proportion of TDR. After correcting for confounding variables, we found a negative correlation between proportion of Alu repeats and mSNP density for 125-1000 kb windows. Similar results were found for the most active subgroup of repeats. In contrast, a negative correlation between proportion of L1 repeats and mSNP density was found only in the larger 1000 kb windows. Using methylation data on germ cells (sperm) from the Human Epigenome Project, we found a lower proportion of Alu repeats adjacent (3-15 kb) to hypermethylated amplicons. On the contrary, there was a higher proportion of L1 repeats in the 3-5 kb of sequence flanking hypermethylated amplicons but not in the 10-15 kb flanks. Our data indicate a differential response to the major repeat families and that DNA methylation is unlikely to be a uniform global defense system against all TDR. It appears to play a role for the L1 subgroup, with sequences adjacent to L1 repeats methylated in response to their proximity. In contrast, sequences adjacent to Alu repeats appear to be hypomethylated, arguing against a role of methylation in germline defense against those elements.
转座子衍生重复序列（TDR）与人类种系甲基化之间可能存在关联，因为许多基因都被 TDR 包围，而甲基化可能会影响附近基因的表达。此外，有人提出 DNA 甲基化是一种针对 TDR 威胁的基因组不稳定性的全局防御机制。我们研究了 HapMap 甲基化相关单核苷酸多态性（mSNP）密度（种系甲基化的标志物）与 TDR 比例之间的相关性。在对混杂变量进行校正后，我们发现 Alu 重复序列比例与 125-1000kb 窗口的 mSNP 密度之间存在负相关。对于最活跃的重复亚群，也得到了类似的结果。相比之下，只有在较大的 1000kb 窗口中才发现 L1 重复序列比例与 mSNP 密度之间存在负相关。利用人类表观基因组计划中关于生殖细胞（精子）的甲基化数据，我们发现，在高度甲基化的扩增子附近（3-15kb），Alu 重复序列的比例较低。相反，在高度甲基化的扩增子侧翼的 3-5kb 序列中，L1 重复序列的比例较高，但在 10-15kb 侧翼中没有。我们的数据表明，不同的重复家族会产生不同的反应，而且 DNA 甲基化不太可能是针对所有 TDR 的统一全局防御系统。它似乎对 L1 亚群起作用，L1 重复序列附近的序列因靠近 L1 重复序列而被甲基化。相比之下，Alu 重复序列附近的序列似乎呈低甲基化状态，这表明甲基化在种系防御这些元件方面没有作用。
