Chromatin condensation is not associated with apoptosis
Chromatin condensation is not associated with apoptosis
复制标题
DOI：
10.1074/jbc.273.38.24470
复制
发表时间：
1998-09-18
影响因子：
4.8
通讯作者：
Th'ng, JPH
中科院分区：
文献类型：
--
作者：
Hendzel, MJ;Nishioka, WK;Th'ng, JPH
细胞凋亡在生物体的生存中扮演着重要的角色，人们已经做了大量的工作来了解调控这一过程的信号通路。染色质组织的特征性变化伴随着细胞凋亡，通常被用作细胞死亡的标志。我们用间接免疫荧光和电子光谱成像技术检测了PC12和HeLa细胞凋亡过程中染色质的结构。我们的结果表明，在有丝分裂过程中通常出现的从头开始的染色质凝聚，在细胞发生凋亡时不会发生。相反，通常观察到的浓缩染色质是异染色质聚集的结果。我们提出的证据表明，在细胞凋亡的早期，含有高乙酰化组蛋白的核酸酶敏感常染色质迅速降解。这与核层降解和核内蛋白基质重组导致的核完整性丧失不谋而合。这些事件导致细胞核塌陷和异染色质聚集，产生浓缩的凋亡染色质的出现。这种异染色质聚集体随后被核酸酶消化，产生寡核体DNA梯形，这是晚期细胞凋亡的标志。与有丝分裂不同，我们没有看到任何证据表明需要磷酸化组蛋白H1和H3来维持染色质浓缩状态。
Apoptosis plays an important role in the survival of an organism, and substantial work has been done to understand the signaling pathways that regulate this process. Characteristic changes in chromatin organization accompany apoptosis and are routinely used as markers for cell death. We have examined the organization of chromatin in apoptotic PC12 and HeLa cells by indirect immunofluorescence and electron spectroscopic imaging. Our results indicate that de novo chromatin condensation normally seen during mitosis does not occur when cells undergo apoptosis. Instead, the condensed chromatin typically observed results from aggregation of the heterochromatin. We present evidence that, early in apoptosis, there is a rapid degradation of the nuclease-hypersensitive euchromatin that contains hyperacetylated histones. This occurs coincident with the loss of nuclear integrity due to degradation of lamins and reorganization of intranuclear protein matrix. These events lead to collapse of the nucleus and aggregation of heterochromatin to produce the appearance of condensed apoptotic chromatin. This heterochromatin aggregate is then digested by nucleases to produce the oligonucleosomal DNA ladder that is a hallmark of late apoptosis. Unlike mitosis, we have not seen any evidence for the requirement of phosphorylated histones H1 and H3 to maintain the chromatin in the condensed state.