Kilobase Pair Chromatin Fiber Contacts Promoted by Living-System-Like DNA Linker Length Distributions and Nucleosome Depletion
Kilobase Pair Chromatin Fiber Contacts Promoted by Living-System-Like DNA Linker Length Distributions and Nucleosome Depletion
复制标题
类似生命系统的 DNA 连接子长度分布和核小体耗竭促进千碱基对染色质纤维接触
DOI：
10.1021/acs.jpcb.7b00998
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发表时间：
2017-04-20
影响因子：
3.3
通讯作者：
Schlick, Tamar
中科院分区：
文献类型：
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作者：
Bascom, Gavin D.;Kim, Taejin;Schlick, Tamar
核小体的位置，或DNA连接体的长度模式，被认为在染色质纤维中产生特定的空间特征，但细节尚不清楚。在这里，我们通过中尺度模型研究了千碱基（kb）范围接触和纤维环是如何依赖于连接体长度（从18到45 bp）的，其值是根据生命系统建模的，包括核小体自由区（NFRs）和基因编码段。我们还比较了在18- 72bp范围内交替分布与随机分布连接长度的人工构建体。研究表明，非均匀分布的NFRs增强了灵活性，并鼓励了kb范围的接触。相邻基因片段之间的NFRs减少了两侧核小体之间的短距离接触，而通过分层环增强了kb范围的接触。我们还证明了接头长度的差异增强了这种接触。特别是，中等大小的光纤连接器长度变化（类似于27 bp）鼓励在随机分布的连接器长度光纤中进行远距离接触。我们的工作强调了连接体长度模式以及结合蛋白在生物调控中的重要性。kb范围染色质折叠形成的接触对基因活性至关重要。因为我们发现生命系统中特殊的连接子长度分布促进了kb的接触，我们的工作提出了操纵这些模式来调节基因活性的方法。
Nucleosome placement, or DNA linker length patterns, are believed to yield specific spatial features in chromatin fibers, but details are unknown. Here we examine by mesoscale modeling how kilobase (kb) range contacts and fiber looping depend on linker lengths ranging from 18 to 45 bp, with values modeled after living systems, including nucleosome free regions (NFRs) and gene encoding segments. We also compare artificial constructs with alternating versus randomly distributed linker lengths in the range of 18-72 bp. We show that nonuniform distributions with NFRs enhance flexibility and encourage kb-range contacts. NFRs between neighboring gene segments diminish short-range contacts between flanking nucleosomes, while enhancing kb-range contacts via hierarchical looping. We also demonstrate that variances in linker lengths enhance such contacts. In particular, moderate sized variations in fiber linker lengths (similar to 27 bp) encourage long-range contacts in randomly distributed linker length fibers. Our work underscores the importance of linker length patterns, alongside bound proteins, in biological regulation. Contacts formed by kb range chromatin folding are crucial to gene activity. Because we find that special linker length distributions in living systems promote kb contacts, our work suggests ways to manipulate these patterns for regulation of gene activity.