DNA thermodynamic stability and supercoil dynamics determine the gene expression program during the bacterial growth cycle.

DNA thermodynamic stability and supercoil dynamics determine the gene expression program during the bacterial growth cycle.
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DOI:
10.1039/c3mb25515h
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发表时间:
2013-06
影响因子:
--
通讯作者:
Patrick Sobetzko;M. Glinkowska;A. Travers;G. Muskhelishvili
Patrick Sobetzko;M. Glinkowska;A. Travers;G. Muskhelishvili
中科院分区:
生物3区
文献类型:
--
作者:
Patrick Sobetzko;M. Glinkowska;A. Travers;G. Muskhelishvili

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构成细胞遗传物质的染色体DNA聚合物主要是编码信息的装置。虽然基因序列包含数字(不连续)线性密码,但DNA超螺旋密度的生理变化产生了额外的模拟(连续)三维信息,这些信息对于染色体压缩和基因表达的调节至关重要。深入了解DNA模拟信息与数字线性密码之间的关系对于理解遗传调控具有重要意义。我们之前对模式生物大肠杆菌的研究表明,与DNA复制相关的染色体基因顺序和DNA超螺旋度的时空梯度决定了生长阶段依赖性基因的转录。在这项研究中,我们揭示了与染色体复制极性相关的DNA热力学稳定性的一般梯度,并体现在细菌生长周期中基因转录的时空模式中。此外,通过整合转录序列的物理和动态特征及其功能内容,我们确定了包含不同功能的基因表达的时空域。因此,我们提供了对细菌生长程序的组织原理和探索染色体动力学的新颖整体方法的见解。
The chromosomal DNA polymer constituting the cellular genetic material is primarily a device for coding information. Whilst the gene sequences comprise the digital (discontinuous) linear code, physiological alterations of the DNA superhelical density generate in addition analog (continuous) three-dimensional information essential for regulation of both chromosome compaction and gene expression. Insight into the relationship between the DNA analog information and the digital linear code is of fundamental importance for understanding genetic regulation. Our previous study in the model organism Escherichia coli suggested that the chromosomal gene order and a spatiotemporal gradient of DNA superhelicity associated with DNA replication determine the growth phase-dependent gene transcription. In this study we reveal a general gradient of DNA thermodynamic stability correlated with the polarity of chromosomal replication and manifest in the spatiotemporal pattern of gene transcription during the bacterial growth cycle. Furthermore, by integrating the physical and dynamic features of the transcribed sequences with their functional content we identify spatiotemporal domains of gene expression encompassing different functions. We thus provide both an insight into the organisational principle of the bacterial growth program and a novel holistic methodology for exploring chromosomal dynamics.