美国托马斯-杰弗逊大学Alexander Mazo小组发现,RNA聚合酶II在DNA复制过程中与活跃基因结合。2023年7月19日,《自然》杂志在线发表了这项成果。
研究人员发现,在通过复制叉后,RNA聚合酶II(Pol II)立即与其他一般转录蛋白和未成熟RNA结合,与新生DNA的前导链和滞后链上的活跃基因重新结合,并迅速恢复转录。这表明,转录活跃的Pol II复合物被保留在DNA附近,而Pol II-PCNA相互作用可能是这种保留的基础。这些发现表明,在从DNA复制到恢复转录的过渡过程中,Pol II机器可能不需要表观遗传标记就能被招募到新合成的DNA上。
据了解,人们认为转录机器在复制过程中会与DNA分离。某些被称为表观遗传标记的蛋白质必须从亲代DNA链转移到子代DNA链,以保持对转录状态的记忆。这些蛋白质被认为能重新启动染色质结构的重建,最终将Pol II招募到新复制的子代链上。人们认为,只有在染色质重建后,Pol II才会被重新招募到活跃基因上。然而,对于Pol II何时以及如何被招募回子链并恢复转录这一核心问题,几乎没有实验证据。
附:英文原文
Title: RNA polymerase II associates with active genes during DNA replication
Author: Fenstermaker, Tyler K., Petruk, Svetlana, Kovermann, Sina K., Brock, Hugh W., Mazo, Alexander
Issue&Volume: 2023-07-19
Abstract: The transcriptional machinery is thought to dissociate from DNA during replication. Certain proteins, termed epigenetic marks, must be transferred from parent to daughter DNA strands in order to maintain the memory of transcriptional states1,2. These proteins are believed to re-initiate rebuilding of chromatin structure, which ultimately recruits RNA polymerase II (Pol II) to the newly replicated daughter strands. It is believed that Pol II is recruited back to active genes only after chromatin is rebuilt3,4. However, there is little experimental evidence addressing the central questions of when and how Pol II is recruited back to the daughter strands and resumes transcription. Here we show that immediately after passage of the replication fork, Pol II in complex with other general transcription proteins and immature RNA re-associates with active genes on both leading and lagging strands of nascent DNA, and rapidly resumes transcription. This suggests that the transcriptionally active Pol II complex is retained in close proximity to DNA, with a Pol II–PCNA interaction potentially underlying this retention. These findings indicate that the Pol II machinery may not require epigenetic marks to be recruited to the newly synthesized DNA during the transition from DNA replication to resumption of transcription.
DOI: 10.1038/s41586-023-06341-9
Source: https://www.nature.com/articles/s41586-023-06341-9
Nature:《自然》,创刊于1869年。隶属于施普林格·自然出版集团,最新IF:69.504
官方网址:http://www.nature.com/
投稿链接:http://www.nature.com/authors/submit_manuscript.html