Nucleosome Breathing Facilitates the Search for Hidden DNA Sites by Pioneer Transcription Factors
Nucleosome Breathing Facilitates the Search for Hidden DNA Sites by Pioneer Transcription Factors
复制标题
核小体呼吸促进先锋转录因子寻找隐藏的 DNA 位点
DOI：
10.1021/acs.jpclett.3c00529
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发表时间：
2023
期刊：
影响因子：
--
通讯作者：
Kolomeisky, Anatoly B.
中科院分区：
文献类型：
--
作者：
Mondal, Anupam;Felipe, Cayke;Kolomeisky, Anatoly B.
遗传信息的传递始于转录因子（TF）与DNA上的特定位点结合。但在活细胞中，DNA大部分被核小体覆盖。有一些蛋白质，被称为先驱TF，可以有效地到达核小体隐藏的DNA位点，尽管其潜在的机制还不清楚。利用最近提出的相互作用补偿机制的思想，我们建立了一个具有核小体呼吸的DNA靶点搜索的随机模型。研究发现，与没有呼吸的情况相比，核小体呼吸可以显着加速先驱TF的搜索。我们认为这是相互作用补偿机制的结果，该机制允许蛋白质通过外部DNA片段进入内部核小体区域。这表明，自然优化先锋TF利用核小体呼吸。所提出的理论图像提供了一个可能的微观解释核小体埋藏的基因的成功入侵。
Transfer of genetic information starts with transcription factors (TFs) binding to specific sites on DNA. But in living cells, DNA is mostly covered by nucleosomes. There are proteins, known as pioneer TFs, that can efficiently reach the DNA sites hidden by nucleosomes, although the underlying mechanisms are not understood. Using the recently proposed idea of interaction-compensation mechanism, we develop a stochastic model for the target search on DNA with nucleosome breathing. It is found that nucleosome breathing can significantly accelerate the search by pioneer TFs in comparison to situations without breathing. We argue that this is the result of the interaction-compensation mechanism that allows proteins to enter the inner nucleosome region through the outer DNA segment. It is suggested that nature optimized pioneer TFs to take advantage of nucleosome breathing. The presented theoretical picture provides a possible microscopic explanation for the successful invasion of nucleosome-buried genes.