衰老相关异染色质聚集——细胞衰老生物学新标志

染色质重塑是调控基因时序性表达的重要环节.衰老的人二倍体成纤维细胞核中有呈点状聚集的异染色质结构,这种特征性现象被称为衰老相关异染色质聚集(SAHF).K9M-H3和HP1是SAHF的标志性蛋白.在SAHF的形成过程中,p16INK4a/Rb途径和高迁移率蛋白A(high-mobility group A protein,HMGA protein)等许多因素起着非常重要的作用.最近研究表明,SAHF能够抑制E2F靶基因的表达,从而使细胞维持于稳定的衰老状态.SAHF的发现为细胞衰老的研究提供了一个新的生物学标志,并为细胞衰老状态的稳定维持提出了一种分子机制.

SAHF: A New Biomarker of Cellular Senescence

The remodeling of chromatin is a key step in controlling and regulating the temporal expression of genes. In the senescent human diploid fibroblast, there is a specific heterochromatic structure accumulating in the nucleus in the form of punctate foci, which is termed as senescence-associated heterochromatic foci (SAHF). The histone H3 methylated on lysine 9 (K9M-H3) and Heterochromatin Protein 1(HP1) are the marker proteins of SAHF. During the process of SAHF formation, many factors such as p16INK4a/Rb pathway and HMGA proteins play a very important role. Recent studies have shown that SAHF may suppress the expression of some E2F-target genes, thereby making the cell keep in a stable senescent state. The discovery of SAHF has provided a new biomarker for the research of cellular senescence, and it also gives us a molecular explanation for the stability of the senescent state.