Ottaviani Alexandre, Gilson Eric, Magdinier Frédérique
Laboratoire de Biologie Moléculaire de la Cellule, CNRS UMR5239, Ecole Normale Supérieure de Lyon, UCBL1, IFR128, 46 allée d'Italie, 69364 Lyon Cedex 07, France.
Biochimie. 2008 Jan;90(1):93-107. doi: 10.1016/j.biochi.2007.07.022. Epub 2007 Aug 6.
Alteration of the epigenome is associated with a wide range of human diseases. Therefore, deciphering the pathways that regulate the epigenetic modulation of gene expression is a major milestone for the understanding of diverse biological mechanisms and subsequently human pathologies. Although often evoked, little is known on the implication of telomeric position effect, a silencing mechanism combining telomere architecture and classical heterochromatin features, in human cells. Nevertheless, this particular silencing mechanism has been investigated in different organisms and several ingredients are likely conserved during evolution. Subtelomeres are highly dynamic regions near the end of the chromosomes that are prone to recombination and may buffer or facilitate the spreading of silencing that emanates from the telomere. Therefore, the composition and integrity of these regions also concur to the propensity of telomeres to regulate the expression, replication and recombination of adjacent regions. Here we describe the similarities and disparities that exist among the different species at chromosome ends with regard to telomeric silencing regulation with a special accent on its implication in numerous human pathologies.
表观基因组的改变与多种人类疾病相关。因此，破译调控基因表达表观遗传调控的途径是理解多种生物学机制以及后续人类病理学的一个重要里程碑。尽管端粒位置效应（一种将端粒结构与经典异染色质特征相结合的沉默机制）常被提及，但在人类细胞中其作用却知之甚少。然而，这种特殊的沉默机制已在不同生物体中得到研究，并且一些成分在进化过程中可能是保守的。亚端粒是染色体末端附近高度动态的区域，容易发生重组，可能缓冲或促进从端粒发出的沉默扩散。因此，这些区域的组成和完整性也有助于端粒调节相邻区域的表达、复制和重组的倾向。在这里，我们描述了不同物种在染色体末端关于端粒沉默调控方面存在的异同，特别强调了其在众多人类病理学中的作用。
