Histone Depletion Facilitates Chromatin Loops on the Kilobasepair Scale
Histone Depletion Facilitates Chromatin Loops on the Kilobasepair Scale
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DOI：
10.1016/j.bpj.2010.08.039
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发表时间：
2010-11-03
影响因子：
3.4
通讯作者：
Heermann, Dieter W.
中科院分区：
文献类型：
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作者：
Diesinger, Philipp M.;Kunkel, Susanne;Heermann, Dieter W.
真核生物DNA在细胞核中的包装对其功能具有决定性作用;例如，基因组远端位点之间的接触构成了基因调控的基本特征。调节蛋白、DNA结合和转录激活之间的相互作用通过间插染色质的成环来促进。这种长程相互作用依赖于染色质的弯曲柔性，即，闭环概率是聚合物柔性的直接可测量的指标。蠕虫状链模型对裸DNA的适用性已被广泛接受。然而，这个模型是否也足以描述真核细胞间期染色质的灵活性仍然是一个讨论的问题。在这里，我们比较了5C数据从基因沙漠和荧光原位杂交的染色质纤维的Monte Carlo模拟结果与组蛋白耗尽和不。然后，我们估计环闭合概率的模拟纤维与估计从分析计算和蠕虫状链模型严重低估了染色质的灵活性急剧弯曲。最重要的是，我们发现，只有纤维的连接组蛋白或核小体的随机损耗可以解释随机染色质接触的概率在小的长度尺度上发挥重要作用的基因调控。可能缺失的连接体组蛋白和核小体不仅仅是简单的、不可避免的、随机发生的缺陷，而是在基因表达中起着调节作用。
The packing of eukaryotic DNA in the nucleus is decisive for its function; for instance, contact between remote genome sites constitutes a basic feature of gene regulation. Interactions among regulatory proteins, DNA binding, and transcription activation are facilitated by looping of the intervening chromatin. Such long-range interactions depend on the bending flexibility of chromatin, i.e., the ring-closure probability is a directly measurable indicator of polymer flexibility. The applicability of a wormlike chain model to naked DNA has been widely accepted. However, whether this model also suffices to describe the flexibility of eukaryotic interphase chromatin is still a matter of discussion. Here we compare both 5C data from a gene desert and data from fluorescence in situ hybridization with the results of a Monte Carlo simulation of chromatin fibers with and without histone depletion. We then estimate the ring-closure probabilities of simulated fibers with estimates from analytical calculations and show that the wormlike chain model grossly underestimates chromatin flexibility for sharp bends. Most importantly, we find that only fibers with random depletion of linker histones or nucleosomes can explain the probability of random chromatin contacts on small length scales that play an important role in gene regulation. It is possible that missing linker histones and nucleosomes are not just simple, unavoidable, randomly occurring defects, but instead play a regulatory role in gene expression.