Jachowicz Joanna W, Torres-Padilla Maria-Elena
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM U964, Université de Strasbourg, 67404, Illkirch, France.
Chromosoma. 2016 Mar;125(1):29-39. doi: 10.1007/s00412-015-0520-2. Epub 2015 May 16.
Approximately half of the mammalian genome is composed of repetitive elements, including LINE-1 (L1) elements. Because of their potential ability to transpose and integrate into other regions of the genome, their activation represents a threat to genome stability. Molecular pathways have emerged to tightly regulate and repress their transcriptional activity, including DNA methylation, histone modifications, and RNA pathways. It has become evident that Line-L1 elements are evolutionary diverse and dedicated repression pathways have been recently uncovered that discriminate between evolutionary old and young elements, with RNA-directed silencing mechanisms playing a prominent role. During periods of epigenetic reprogramming in development, specific classes of repetitive elements are upregulated, presumably due to the loss of most heterochromatic marks in this process. While we have learnt a lot on the molecular mechanisms that regulate Line-L1 expression over the last years, it is still unclear whether reactivation of Line-L1 after fertilization serves a functional purpose or it is a simple side effect of reprogramming.
大约一半的哺乳动物基因组由重复元件组成,包括1型长散在核元件(LINE-1,L1)。由于它们具有转座并整合到基因组其他区域的潜在能力,其激活对基因组稳定性构成威胁。已经出现了一些分子途径来严格调控和抑制它们的转录活性,包括DNA甲基化、组蛋白修饰和RNA途径。很明显,L1元件在进化上是多样的,最近发现了专门的抑制途径,可区分进化上古老和年轻的元件,其中RNA定向沉默机制发挥着重要作用。在发育过程中的表观遗传重编程期间,特定类别的重复元件会上调,这可能是由于在此过程中大多数异染色质标记的丢失。虽然在过去几年里我们对调控L1表达的分子机制了解很多,但受精后L1的重新激活是具有功能目的还是仅仅是重编程的一个简单副作用仍不清楚。