Poot Raymond A, Bozhenok Ludmila, van den Berg Debbie L C, Steffensen Søren, Ferreira Fernando, Grimaldi Margaret, Gilbert Nick, Ferreira Joao, Varga-Weisz Patrick D
Marie Curie Research Institute, The Chart, Oxted, Surrey RH8 0TL, UK.
Nat Cell Biol. 2004 Dec;6(12):1236-44. doi: 10.1038/ncb1196. Epub 2004 Nov 14.
Chromatin states have to be faithfully duplicated during DNA replication to maintain cell identity. It is unclear whether or how ATP-dependent chromatin-remodelling factors are involved in this process. Here we provide evidence that the Williams syndrome transcription factor (WSTF) is targeted to replication foci through direct interaction with the DNA clamp PCNA, an important coordinator of DNA and chromatin replication. WSTF, in turn, recruits imitation switch (ISWI)-type nucleosome-remodelling factor SNF2H to replication sites. These findings reveal a novel recruitment mechanism for ATP-dependent chromatin-remodelling factors that is fundamentally different from the previously documented targeting by sequence-specific transcriptional regulators. RNA-interference-mediated depletion of WSTF or SNF2H causes a compaction of newly replicated chromatin and increases the amount of heterochromatin markers, including HP1beta. This increase in the amount of HP1beta protein is mediated by progression through S phase and is not the result of an increase in HP1beta mRNA levels. We propose that the WSTF-ISWI complex has a role in the maintenance of chromatin structures during DNA replication.
染色质状态必须在DNA复制过程中被精确复制，以维持细胞特性。目前尚不清楚ATP依赖的染色质重塑因子是否以及如何参与这一过程。在此，我们提供证据表明，威廉姆斯综合征转录因子（WSTF）通过与DNA钳PCNA直接相互作用靶向复制灶，PCNA是DNA和染色质复制的重要协调因子。反过来，WSTF招募模仿开关（ISWI）型核小体重塑因子SNF2H到复制位点。这些发现揭示了一种ATP依赖的染色质重塑因子的新型招募机制，该机制与先前记录的序列特异性转录调节因子的靶向机制有根本不同。RNA干扰介导的WSTF或SNF2H缺失会导致新复制染色质的压缩，并增加包括HP1β在内的异染色质标记物的数量。HP1β蛋白数量的这种增加是由S期进程介导的，而不是HP1β mRNA水平增加的结果。我们提出，WSTF-ISWI复合物在DNA复制过程中对染色质结构的维持起作用。
