Chromatin contributes to structural integrity of promyelocytic leukemia bodies through a SUMO-1-independent mechanism
Chromatin contributes to structural integrity of promyelocytic leukemia bodies through a SUMO-1-independent mechanism
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DOI：
10.1074/jbc.m312580200
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发表时间：
2004-03-05
影响因子：
4.8
通讯作者：
Bazett-Jones, DP
中科院分区：
文献类型：
--
作者：
Eskiw, CH;Dellaire, G;Bazett-Jones, DP
早幼粒细胞白血病（PML）蛋白与转录调控、细胞凋亡、DNA修复和肿瘤抑制有关。然而，尚不清楚PML以及PML小体的其他成分是在小体附近还是在核质的其他位置发挥作用。在本研究中，我们证明PML小体周围的染色质组织通过一种不依赖SUMO - 1的机制影响其形态、动力学和结构完整性。在转录抑制后以及早期细胞凋亡期间，染色质从PML小体的周边回缩，与此同时，通过含PML的超分子微体的分裂形成新的含PML结构。微体与亲代PML小体的分裂和融合都表明小体的结构完整性丧失，这取决于周围染色质的状态。用DNA酶I处理活细胞可重现PML小体的结构不稳定性，这一观察结果支持了上述观点。此外，通常被染色质包围且位置稳定的PML小体在这些处理后变得更具动态性，这可能是由于染色质接触的丧失。SUMO - 1是PML小体形成所必需的一种修饰，其过表达并不能阻止PML小体的分裂，这表明PML小体结构基于染色质的完整性是通过一种不依赖SUMO - 1的机制实现的。
Promyelocytic leukemia (PML) protein is implicated in transcriptional regulation, apoptosis, DNA repair, and tumor suppression. It is not known, however, whether PML and other components of PML bodies function within the vicinity of the bodies or elsewhere in the nucleoplasm. In this study, we demonstrate that chromatin organization around PML bodies influences their morphology, dynamics, and structural integrity by a SUMO-1-independent mechanism. Following transcriptional inhibition and during early apoptosis, chromatin retracts from the periphery of PML bodies, coinciding with the formation of new PML-containing structures through fission of supramolecular PML-containing microbodies. Both fission and fusion of microbodies with parental PML bodies indicate a loss of structural integrity of the bodies, dependent on the state of the surrounding chromatin. This is supported by the observation that treatment of live cells with DNase I could reproduce the structural instability of PML bodies. In addition, PML bodies, which are normally surrounded by chromatin and are positionally stable, become more dynamic following these treatments, presumably due to the loss of chromatin contacts. Overexpression of SUMO-1, a modification required for PML body formation, did not prevent PML body fission, indicating that chromatin-based integrity of PML body structure occurs through a SUMO-1-independent mechanism.