Approximately half the mammalian genome is composed of repetitive sequences, and accumulating evidence suggests that some may have an impact on genome function. Here, we characterized a large array class of repeats of long-interspersed elements (LINE-1). Although widely distributed in mammals, locations of such arrays are species specific. Using targeted deletion, we asked whether a 170-kb LINE-1 array located at a mouse imprinted domain might function as a modulator of local transcriptional control. The LINE-1 array is lamina associated in differentiated ES cells consistent with its AT-richness, and although imprinting occurs both proximally and distally to the array, active LINE-1 transcripts within the tract are biallelically expressed. Upon deletion of the array, no perturbation of imprinting was observed, and abnormal phenotypes were not detected in maternal or paternal heterozygous or homozygous mutant mice. The array does not shield nonimprinted genes in the vicinity from local imprinting control. Reduced neural expression of protein-coding genes observed upon paternal transmission of the deletion is likely due to the removal of a brain-specific enhancer embedded within the LINE array. Our findings suggest that presence of a 170-kb LINE-1 array reflects the tolerance of the site for repeat insertion rather than an important genomic function in normal development.

大约一半的哺乳动物基因组由重复序列组成，越来越多的证据表明其中一些可能对基因组功能产生影响。在这里，我们描述了长散布元素重复的大型数组类 (LINE-1)。尽管广泛分布在哺乳动物中，但这种阵列的位置是特定于物种的。使用定向删除，我们询问位于小鼠印记结构域的 170 kb LINE-1 阵列是否可以充当局部转录控制的调节器。 LINE-1 阵列是与分化的 ES 细胞相关的层，与其 AT 丰富度一致，尽管印记发生在阵列的近端和远端，但该束内的活性 LINE-1 转录物是双等位基因表达的。删除阵列后，没有观察到印记的扰动，并且在母本或父本杂合或纯合突变小鼠中未检测到异常表型。该阵列不会屏蔽附近的非印记基因免受局部印记控制。在父系遗传缺失后观察到的蛋白质编码基因的神经表达减少可能是由于 LINE 阵列中嵌入的大脑特异性增强子被去除所致。我们的研究结果表明，170 kb LINE-1 阵列的存在反映了该位点对重复插入的耐受性，而不是正常发育中重要的基因组功能。