A model for Escherichia coli chromosome packaging supports transcription factor-induced DNA domain formation.

A model for Escherichia coli chromosome packaging supports transcription factor-induced DNA domain formation.
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DOI:
10.1093/nar/gkr779
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发表时间:
2012-02
影响因子:
14.9
通讯作者:
Wiggins PA
Wiggins PA
中科院分区:
生物学2区
文献类型:
--
作者:
Fritsche M;Li S;Heermann DW;Wiggins PA

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什么物理机制导致高度浓缩和限制的环状染色体的组织?计算模型表明,约束诱导的组织是能够克服染色体的倾向,混合形成的拓扑结构域。实验观察到的高精度的单独亚细胞定位的基因座(位于不同的染色体结构域)在大肠杆菌中自然出现的结果熵分层的染色体环。我们提出了一种可能的机制来组织这些域:监管控制定义的基础E。大肠杆菌基因调控网络需要转录因子基因和靶基因的共定位。调查这一假设,我们发现DNA链自组织成几个拓扑结构可区分的域之间的相互作用的熵排斥的染色体环和它们的压缩,由于限制几何形状诱导一个有效的类核顺式结构。因此,我们认为染色体的物理结构是调控相互作用的直接结果。为了重现所观察到的染色体的精确排序,我们估计,域的大小分布在10和700 kb之间,与DNA超螺旋的上下文中确定的拓扑结构域的大小一致。
What physical mechanism leads to organization of a highly condensed and confined circular chromosome? Computational modeling shows that confinement-induced organization is able to overcome the chromosome's propensity to mix by the formation of topological domains. The experimentally observed high precision of separate subcellular positioning of loci (located on different chromosomal domains) in Escherichia coli naturally emerges as a result of entropic demixing of such chromosomal loops. We propose one possible mechanism for organizing these domains: regulatory control defined by the underlying E. coli gene regulatory network requires the colocalization of transcription factor genes and target genes. Investigating this assumption, we find the DNA chain to self-organize into several topologically distinguishable domains where the interplay between the entropic repulsion of chromosomal loops and their compression due to the confining geometry induces an effective nucleoid filament-type of structure. Thus, we propose that the physical structure of the chromosome is a direct result of regulatory interactions. To reproduce the observed precise ordering of the chromosome, we estimate that the domain sizes are distributed between 10 and 700 kb, in agreement with the size of topological domains identified in the context of DNA supercoiling.
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