Partially Assembled Nucleosome Structures at Atomic Detail

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• 作者：Georgy N. Rychkov¹ ; ² ; Andrey V. Ilatovskiy¹ ; ³ ; Igor B. Nazarov⁴ ; Alexey V. Shvetsov¹ ; ⁵ ; Dmitry V. Lebedev¹ ; Alexander Y. Konev¹ ; Vladimir V. Isaev-Ivanov¹ ; Alexey V. Onufriev⁶ ; ^{alexey@cs.vt.edu}
• 刊名：Biophysical Journal
• 出版年：2017
• 出版时间：7 February 2017
• 年：2017
• 卷：112
• 期：3
• 页码：460-472
• 全文大小：2708 K
• 卷排序：112

文摘

The evidence is now overwhelming that partially assembled nucleosome states (PANS) are as important as the canonical nucleosome structure for the understanding of how accessibility to genomic DNA is regulated in cells. We use a combination of molecular dynamics simulation and atomic force microscopy to deliver, in atomic detail, structural models of three key PANS: the hexasome (H2A·H2B)·(H3·H4)2, the tetrasome (H3·H4)2, and the disome (H3·H4). Despite fluctuations of the conformation of the free DNA in these structures, regions of protected DNA in close contact with the histone core remain stable, thus establishing the basis for the understanding of the role of PANS in DNA accessibility regulation. On average, the length of protected DNA in each structure is roughly 18 basepairs per histone protein. Atomistically detailed PANS are used to explain experimental observations; specifically, we discuss interpretation of atomic force microscopy, Förster resonance energy transfer, and small-angle x-ray scattering data obtained under conditions when PANS are expected to exist. Further, we suggest an alternative interpretation of a recent genome-wide study of DNA protection in active chromatin of fruit fly, leading to a conclusion that the three PANS are present in actively transcribing regions in a substantial amount. The presence of PANS may not only be a consequence, but also a prerequisite for fast transcription in vivo.