Epigenetic control of mammalian retrotransposons

我的团队已经建立了一个实验系统来研究重新整合到人类或小鼠染色体上的L1反转录转座子报告子的表观遗传控制。利用这种组织培养系统，我们正在研究通过逆转录转位依赖机制新插入的L1报告基因的杂色和沉默机制。我们还研究了人类和小鼠基因组中L1逆转录转座子的原位表观遗传控制，以及这种控制与各种细胞中L1表达的关系。这些实验作为对“基因组防御模型”的检验，表明DNA甲基化本身并不能解释体细胞组织中L1转录异常强烈的负调控。我们已经成功地对几个完整的基因表达序列分析（SAGE）长标签文库进行了测序和分析，以表征具有改变表观遗传控制的体细胞中的全局转录物水平，包括那些与重复和转座元件相对应的转录物水平。迄今为止完成的文库包括许多以非常高的比率差异表达的转录本。我们现在正在鉴定差异表达的转录本，并进一步表征改变的表达如何与改变的表观遗传控制相关。

My group has established an experimental system to study epigenetic control of L1 retrotransposon reporters integrated de novo into human or mouse chromosomes. Using this tissue culture system, we are studying the mechanism of variegation and silencing of L1 reporters, newly inserted via a retrotransposition-dependent mechanism. We have also studied epigenetic control of L1 retrotransposons in situ in the human and mouse genomes, and the relationship between such control and L1 expression in various cells. These experiments, as a test of the "genome defense model", have shown that DNA methylation does not by itself account for exceptionally strong negative regulation of L1 transcription in somatic tissues.We have successfully sequenced and analyzed several full Serial Analysis of Gene Expression (SAGE) long-tag libraries to characterize global transcript levels, including those corresponding to repetitive and transposable elements, in somatic cells with altered epigenetic controls. The libraries completed to date include numerous transcripts that are differentially expressed at very high ratios. We are now identifying the differentially expressed transcripts and further characterizing how altered expression may be related to changed epigenetic control.