Evidence for short-range helical order in the 30-nm chromatin fibers of erythrocyte nuclei

Evidence for short-range helical order in the 30-nm chromatin fibers of erythrocyte nuclei
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DOI:
10.1073/pnas.1108268108
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发表时间:
2011-10-11
影响因子:
11.1
通讯作者:
Frangakis, Achilleas S.
Frangakis, Achilleas S.
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Scheffer, Margot P.;Eltsov, Mikhail;Frangakis, Achilleas S.

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真核生物的染色质折叠使基因组适合于有限体积的细胞核。高阶染色质结构的形成降低了DNA的可接近性,从而有助于控制基本的基因组功能,如转录、DNA复制和修复。30纳米纤维被认为是染色质折叠的第一个层次,但核小体在30纳米纤维中的排列以前是未知的。我们使用玻璃体切片的低温电子断层扫描来确定鸟类红细胞核致密的天然30纳米纤维的结构。亚层析成像平均显示,30纳米纤维的主要几何形状是一个左旋双起点螺旋,每11纳米约有6.5个核小体,其中核小体面对面并置,但偏离其超螺旋轴,轴向平移约3.4纳米,方位旋转约54度。在垂直于纤维轴的方向观察核小体时,核小体呈棋盘状,但不交叉。纤维内的核小体显示出比先前预期的更大的中心到中心的核小体间距离,从而排除了核到核相互作用的可能性,解释了转录和调节因子如何进入核小体。
Chromatin folding in eukaryotes fits the genome into the limited volume of the cell nucleus. Formation of higher-order chromatin structures attenuates DNA accessibility, thus contributing to the control of essential genome functions such as transcription, DNA replication, and repair. The 30-nm fiber is thought to be the first hierarchical level of chromatin folding, but the nucleosome arrangement in the compact 30-nm fiber was previously unknown. We used cryoelectron tomography of vitreous sections to determine the structure of the compact, native 30-nm fiber of avian erythrocyte nuclei. The predominant geometry of the 30-nm fiber revealed by subtomogram averaging is a left-handed two-start helix with approximately 6.5 nucleosomes per 11 nm, in which the nucleosomes are juxtaposed face-to-face but are shifted off their superhelical axes with an axial translation of approximately 3.4 nm and an azimuthal rotation of approximately 54 degrees. The nucleosomes produce a checkerboard pattern when observed in the direction perpendicular to the fiber axis but are not interdigitated. The nucleosome packing within the fibers shows larger center-to-center internucleosomal distances than previously anticipated, thus excluding the possibility of core-to-core interactions, explaining how transcription and regulation factors can access nucleosomes.