FACT Remodels the Tetranucleosomal Unit of Chromatin Fibers for Gene Transcription

FACT Remodels the Tetranucleosomal Unit of Chromatin Fibers for Gene Transcription
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FACT 重塑染色质纤维的四核小体单位以进行基因转录

DOI:
10.1016/j.molcel.2016.08.024
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发表时间:
2016-10-06
期刊:
影响因子:
16
通讯作者:
Li, Guohong
Li, Guohong
中科院分区:
生物学1区
文献类型:
--
作者:
Li, Wei;Chen, Ping;Li, Guohong

文献摘要

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在真核生物中,基因组 DNA 包装到染色质中在基因调控中发挥着关键作用。然而,染色质纤维的动态组织及其调节机制仍然知之甚少。使用单分子力谱,我们揭示了串上的四核小体在染色质纤维的分层组织过程中表现为稳定的二级结构。在体外,组蛋白伴侣 FACT(促进染色质转录)会减弱四核小体单位的稳定性。与体外观察一致,我们的全基因组分析进一步表明,FACT 通过破坏酵母中染色质纤维四核小体单元的稳定性来促进基因转录。此外,我们发现连接组蛋白 H1 不仅增强了稳定性,而且还促进了外核小体包裹的折叠和展开动力学。我们的研究表明,四核小体是核小体之外的染色质纤维的调节结构单元,并为基因转录过程中染色质纤维的结构和动力学提供了重要的机制见解。
In eukaryotes, the packaging of genomic DNA into chromatin plays a critical role in gene regulation. However, the dynamic organization of chromatin fibers and its regulatory mechanisms remain poorly understood. Using single-molecule force spectroscopy, we reveal that the tetranucleosomes-on-a-string appears as a stable secondary structure during hierarchical organization of chromatin fibers. The stability of the tetranucleosomal unit is attenuated by histone chaperone FACT (facilitates chromatin transcription) in vitro. Consistent with in vitro observations, our genome-wide analysis further shows that FACT facilitates gene transcription by destabilizing the tetranucleosomal unit of chromatin fibers in yeast. Additionally, we found that the linker histone H1 not only enhances the stability but also facilitates the folding and unfolding kinetics of the outer nucleosomal wrap. Our study demonstrates that the tetranucleosome is a regulatory structural unit of chromatin fibers beyond the nucleosome and provides crucial mechanistic insights into the structure and dynamics of chromatin fibers during gene transcription.