Local chromatin fiber folding represses transcription and loop extrusion in quiescent cells.

Local chromatin fiber folding represses transcription and loop extrusion in quiescent cells.
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DOI:
10.7554/elife.72062
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发表时间:
2021-11-04
期刊:
影响因子:
7.7
通讯作者:
Tsukiyama T
Tsukiyama T
中科院分区:
生物学1区
文献类型:
--
作者:
Swygert SG;Lin D;Portillo-Ledesma S;Lin PY;Hunt DR;Kao CF;Schlick T;Noble WS;Tsukiyama T

文献摘要

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一个长期存在的假设是染色质纤维折叠介导的相互作用核小体抑制转录。然而,很难确定细胞中局部染色质纤维压实与转录之间的关系。此外,纤维直径的整体变化尚未观察到,甚至在间期和有丝分裂染色体之间。我们表明,在静止酵母局部核小体间接触范围的增加驱动全基因组染色质纤维的压实。与活跃分裂的细胞不同,静止细胞中的核小体间相互作用需要组蛋白H4尾部的一个基本补丁。这种静止特异性纤维折叠在全局上抑制转录并抑制冷凝蛋白对染色质环的挤压。这些结果揭示了在细胞状态转变过程中染色质纤维压实可能发生全局变化,并确立了局部染色质纤维折叠在调节转录和染色质结构域形成中的生理作用。
A longstanding hypothesis is that chromatin fiber folding mediated by interactions between nearby nucleosomes represses transcription. However, it has been difficult to determine the relationship between local chromatin fiber compaction and transcription in cells. Further, global changes in fiber diameters have not been observed, even between interphase and mitotic chromosomes. We show that an increase in the range of local inter-nucleosomal contacts in quiescent yeast drives the compaction of chromatin fibers genome-wide. Unlike actively dividing cells, inter-nucleosomal interactions in quiescent cells require a basic patch in the histone H4 tail. This quiescence-specific fiber folding globally represses transcription and inhibits chromatin loop extrusion by condensin. These results reveal that global changes in chromatin fiber compaction can occur during cell state transitions, and establish physiological roles for local chromatin fiber folding in regulating transcription and chromatin domain formation.