The dynamic architecture of chromatin fibers, a key determinant of genome regulation, is poorly understood. Here, we employ multimodal single-molecule Förster resonance energy transfer studies to reveal structural states and their interconversion kinetics in chromatin fibers. We show that nucleosomes engage in short-lived (micro- to milliseconds) stacking interactions with one of their neighbors. This results in discrete tetranucleosome units with distinct interaction registers that interconvert within hundreds of milliseconds. Additionally, we find that dynamic chromatin architecture is modulated by the multivalent architectural protein heterochromatin protein 1α (HP1α), which engages methylated histone tails and thereby transiently stabilizes stacked nucleosomes. This compacted state nevertheless remains dynamic, exhibiting fluctuations on the timescale of HP1α residence times. Overall, this study reveals that exposure of internal DNA sites and nucleosome surfaces in chromatin fibers is governed by an intrinsic dynamic hierarchy from micro- to milliseconds, allowing the gene regulation machinery to access compact chromatin.

中文翻译：

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单分子 FRET 揭示了由 HP1α 调节的多尺度染色质动力学。

染色质纤维的动态结构是基因组调控的关键决定因素，人们对此知之甚少。在这里，我们采用多峰单分子 Förster 共振能量转移研究来揭示染色质纤维中的结构状态及其相互转化动力学。我们表明，核小体与其邻居之一进行短暂（微秒到毫秒）的堆叠相互作用。这导致离散的四核小体单元具有不同的相互作用寄存器，可在数百毫秒内相互转换。此外，我们发现动态染色质结构受到多价结构蛋白异染色质蛋白 1α (HP1α) 的调节，HP1α 与甲基化组蛋白尾部结合，从而瞬时稳定堆叠的核小体。这种压缩状态仍然是动态的，在 HP1α 停留时间的时间尺度上表现出波动。总体而言，这项研究表明，染色质纤维中内部 DNA 位点和核小体表面的暴露受到从微秒到毫秒的内在动态层次结构的控制，从而使基因调控机制能够访问紧凑的染色质。