Transcriptional coactivator PC4, a chromatin-associated protein, induces chromatin condensation
Transcriptional coactivator PC4, a chromatin-associated protein, induces chromatin condensation
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DOI：
10.1128/mcb.00887-06
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发表时间：
2006-11-01
影响因子：
5.3
通讯作者：
Kundu, Tapas K.
中科院分区：
文献类型：
--
作者：
Das, Chandrima;Hizume, Kohji;Kundu, Tapas K.
人类转录共激活因子PC4是一种丰富的多功能蛋白，在细胞转录、复制和修复等过程中发挥着多种重要作用。它也是p53功能的独特激活剂。在这里，我们报道了PC4是染色质的真正成分，具有独特的染色质组织能力。PC4在细胞周期的各个阶段主要与染色质相关，除着丝粒外，PC4广泛分布于有丝分裂染色体臂上，呈点状分布。它选择性地与核心组蛋白H3和11213相互作用；这种相互作用对于pc4介导的染色质凝聚至关重要，正如微球菌核酸酶（MNase）可及性分析、圆二色光谱和原子力显微镜（AFM）所证明的那样。AFM图像显示，与连接体组蛋白H1相比，PC4明显压缩了100 kb重组染色质。在HeLa细胞中，PC4表达的沉默导致染色质分解，正如MNase可及性的增加所证明的那样。敲低PC4上调多个基因，导致细胞周期G(2)/M检查点阻滞，提示其作为染色质压缩蛋白的生理作用。这些结果表明PC4是染色质相关蛋白家族的新成员，在染色质组织中起着重要作用。
Human transcriptional coactivator PC4 is a highly abundant multifunctional protein which plays diverse important roles in cellular processes, including transcription, replication, and repair. It is also a unique activator of p53 function. Here we report that PC4 is a bona fide component of chromatin with distinct chromatin organization ability. PC4 is predominantly associated with the chromatin throughout the stages of cell cycle and is broadly distributed on the mitotic chromosome arms in a punctate manner except for the centromere. It selectively interacts with core histones H3 and 11213; this interaction is essential for PC4-mediated chromatin condensation, as demonstrated by micrococcal nuclease (MNase) accessibility assays, circular dichroism spectroscopy, and atomic force microscopy (AFM). The AFM images show that PC4 compacts the 100-kb reconstituted chromatin distinctly compared to the results seen with the linker histone H1. Silencing of PC4 expression in HeLa cells results in chromatin decompaction, as evidenced by the increase in MNase accessibility. Knocking down of PC4 up-regulates several genes, leading to the G(2)/M checkpoint arrest of cell cycle, which suggests its physiological role as a chromatin-compacting protein. These results establish PC4 as a new member of chromatin-associated protein family, which plays an important role in chromatin organization.