Brenner C, Fuks F
Laboratory of Molecular Virology, Faculty of Medicine, Free University of Brussels, Belgium.
Curr Top Microbiol Immunol. 2006;301:45-66. doi: 10.1007/3-540-31390-7_3.
DNA methylation plays a pivotal role during development in mammals and is central to transcriptional silencing. The DNA methyltransferases (DNMTs) are responsible for the generation of genomic methylation patterns leading to gene silencing, but the underlying molecular basis remains largely shrouded in mystery. Here we review our current understanding of the mechanisms by which DNMTs repress transcription and how they are targeted to preferred DNA sequences. Emerging evidence points to an essential and intricate web of interactions between DNMTs and the chromatin environment in which they function. The recent identification of novel transcription factors recruiting the DNMTs may open new avenues of research into the origin of DNA methylation patterns. Thanks to these emerging clues, researchers have begun to lift the veil on the multi-faceted DNMTs, but there remains fascinating work ahead for whoever wants to fully understand DNMTs and their role in the mammalian cell.
DNA甲基化在哺乳动物发育过程中起着关键作用，是转录沉默的核心。DNA甲基转移酶（DNMTs）负责产生导致基因沉默的基因组甲基化模式，但其潜在的分子基础在很大程度上仍笼罩在神秘之中。在这里，我们回顾了我们目前对DNMTs抑制转录的机制以及它们如何靶向特定DNA序列的理解。新出现的证据表明，DNMTs与其发挥作用的染色质环境之间存在着一个基本且复杂的相互作用网络。最近对招募DNMTs的新型转录因子的鉴定可能为研究DNA甲基化模式的起源开辟新的途径。由于这些新出现的线索，研究人员已经开始揭开多面的DNMTs的面纱，但对于任何想要全面了解DNMTs及其在哺乳动物细胞中的作用的人来说，前方仍有引人入胜的工作要做。
