Fraga Mario F, Esteller Manel
Cancer Epigenetics Laboratory, Spanish National Cancer Centre (CNIO), Melchor Fernandez Almagro 3, 28029 Madrid, Spain.
Trends Genet. 2007 Aug;23(8):413-8. doi: 10.1016/j.tig.2007.05.008. Epub 2007 Jun 7.
'Aging epigenetics' is an emerging field that promises exciting revelations in the near future. Here we focus on the functional and biological significance of the epigenetic alterations that accumulate during aging and are important in tumorigenesis. Paradigmatic examples are provided by the global loss of DNA methylation in aging and cancer and by the promoter hypermethylation of genes with a dual role in tumor suppression and progeria, such as the Werner syndrome (WRN) and lamin A/C genes. Another twist is provided by sirtuins, a family of NAD-dependent deacetylases that act on Lys16 of histone H4, which are emerging as a link between cellular transformation and lifespan.
“衰老表观遗传学”是一个新兴领域,有望在不久的将来带来令人兴奋的新发现。在这里,我们关注衰老过程中积累的表观遗传改变的功能和生物学意义,这些改变在肿瘤发生中很重要。衰老和癌症中DNA甲基化的整体缺失,以及在肿瘤抑制和早衰中具有双重作用的基因(如沃纳综合征(WRN)和核纤层蛋白A/C基因)的启动子高甲基化,就是典型的例子。另一个新情况是沉默调节蛋白,这是一类作用于组蛋白H4赖氨酸16位点的NAD依赖性脱乙酰酶,它们正成为细胞转化与寿命之间的一个联系。