Chromatin fiber polymorphism triggered by variations of DNA linker lengths
Chromatin fiber polymorphism triggered by variations of DNA linker lengths
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DOI：
10.1073/pnas.1315872111
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发表时间：
2014-06-03
影响因子：
11.1
通讯作者：
Schlick, Tamar
中科院分区：
文献类型：
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作者：
Collepardo-Guevara, Rosana;Schlick, Tamar
破译控制染色质纤维结构的因素是理解基本染色体过程的关键。虽然细节仍然未知，但越来越清楚的是，染色质是多态性的，取决于内部和外部因素。特别是，连接连续核小体的不同长度的接头DNA（以核小体重复长度或NRL测量）表征不同的细胞类型和细胞周期阶段，产生不同的结构。NRL在单个纤维内也是不均匀的，但这种多样性如何影响染色质纤维结构尚不清楚。在这里，我们进行Monte Carlo模拟的粗粒度的染色体模型，以帮助解释纤维结构受到纤维内NRL的变化，有关增殖细胞的间期染色质，纤维重塑因子，和调控DNA序列。我们发现，纤维内NRL变化对染色质结构有着深远的影响，出现了各种不同的架构（高度弯曲的窄形式，规范和不规则的锯齿形纤维，和多态性构象），这取决于混合的NRL。这种广泛的纤维形式的稳定性可能允许NRL变化来调节纤维压实和选择性DNA暴露。从规范到急剧弯曲的结构，如发夹和环，多晶型形式产生于大的NRL变化，并且令人惊讶地比均匀的NRL结构更紧凑。除了典型的30 nm纤维的近核小体相互作用外，它们还通过尾介导的远核小体相互作用来区分。多态性与染色质的多样性生物学功能和异质性成分是一致的。纤维内NRL的变化，特别是，可能有助于纤维弯曲和循环，从而在相关的监管过程中的远程通信。
Deciphering the factors that control chromatin fiber structure is key to understanding fundamental chromosomal processes. Although details remain unknown, it is becoming clear that chromatin is polymorphic depending on internal and external factors. In particular, different lengths of the linker DNAs joining successive nucleosomes (measured in nucleosome-repeat lengths or NRLs) that characterize different cell types and cell cycle stages produce different structures. NRL is also nonuniform within single fibers, but how this diversity affects chromatin fiber structure is not clear. Here we perform Monte Carlo simulations of a coarse-grained oligonucleosome model to help interpret fiber structure subject to intrafiber NRL variations, as relevant to proliferating cells of interphase chromatin, fibers subject to remodeling factors, and regulatory DNA sequences. We find that intrafiber NRL variations have a profound impact on chromatin structure, with a wide range of different architectures emerging (highly bent narrow forms, canonical and irregular zigzag fibers, and polymorphic conformations), depending on the NRLs mixed. This stabilization of a wide range of fiber forms might allow NRL variations to regulate both fiber compaction and selective DNA exposure. The polymorphic forms spanning canonical to sharply bent structures, like hairpins and loops, arise from large NRL variations and are surprisingly more compact than uniform NRL structures. They are distinguished by tail-mediated far-nucleosome interactions, in addition to the near-nucleosome interactions of canonical 30-nm fibers. Polymorphism is consistent with chromatin's diverse biological functions and heterogeneous constituents. Intrafiber NRL variations, in particular, may contribute to fiber bending and looping and thus to distant communication in associated regulatory processes.