Schoeftner Stefan, Blasco Maria A
Telomeres and Telomerase Group, Molecular Oncology Program, Spanish National Cancer Research Centre (CNIO), Madrid, Spain.
EMBO J. 2009 Aug 19;28(16):2323-36. doi: 10.1038/emboj.2009.197. Epub 2009 Jul 23.
Protection of chromosome ends from DNA repair and degradation activities is mediated by specialized protein complexes bound to telomere repeats. Recently, it has become apparent that epigenetic regulation of the telomeric chromatin template critically impacts on telomere function and telomere-length homeostasis from yeast to man. Across all species, telomeric repeats as well as the adjacent subtelomeric regions carry features of repressive chromatin. Disruption of this silent chromatin environment results in loss of telomere-length control and increased telomere recombination. In turn, progressive telomere loss reduces chromatin compaction at telomeric and subtelomeric domains. The recent discoveries of telomere chromatin regulation during early mammalian development, as well as during nuclear reprogramming, further highlights a central role of telomere chromatin changes in ontogenesis. In addition, telomeres were recently shown to generate long, non-coding RNAs that remain associated to telomeric chromatin and will provide new insights into the regulation of telomere length and telomere chromatin. In this review, we will discuss the epigenetic regulation of telomeres across species, with special emphasis on mammalian telomeres. We will also discuss the links between epigenetic alterations at mammalian telomeres and telomere-associated diseases.
染色体末端免受DNA修复和降解活动的影响是由与端粒重复序列结合的特殊蛋白质复合物介导的。最近，很明显，从酵母到人类，端粒染色质模板的表观遗传调控对端粒功能和端粒长度稳态有着至关重要的影响。在所有物种中，端粒重复序列以及相邻的亚端粒区域都具有抑制性染色质的特征。这种沉默染色质环境的破坏会导致端粒长度控制的丧失和端粒重组的增加。反过来，端粒的逐渐丢失会降低端粒和亚端粒区域的染色质压缩。最近在早期哺乳动物发育以及核重编程过程中端粒染色质调控的发现，进一步凸显了端粒染色质变化在个体发育中的核心作用。此外，最近发现端粒能产生与端粒染色质保持相关的长链非编码RNA，这将为端粒长度和端粒染色质的调控提供新的见解。在这篇综述中，我们将讨论跨物种端粒的表观遗传调控，特别强调哺乳动物端粒。我们还将讨论哺乳动物端粒的表观遗传改变与端粒相关疾病之间的联系。
