Transcription modulates chromatin dynamics and locus configuration sampling.
Transcription modulates chromatin dynamics and locus configuration sampling.
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DOI：
10.1038/s41594-023-01059-8
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发表时间：
2023-09
影响因子：
16.8
通讯作者：
Brackley, Chris A. A.
中科院分区：
文献类型：
--
作者：
Forte, Giada;Buckle, Adam;Boyle, Shelagh;Marenduzzo, Davide;Gilbert, Nick;Brackley, Chris A. A.
在活细胞中，基因位点的3D结构是动态的，但在固定样品中的3C和FISH实验并没有揭示这一点，这在我们的理解中留下了显着的差距。为了克服这些局限性，我们应用高度预测的异形聚合物（HiP-HoP）模型，以确定在Pax 6基因座的染色质纤维迁移率在三个小鼠细胞系具有不同的转录状态。虽然转录活性对40 kbp区域的运动影响最小，但我们观察到较小的1 kbp区域的运动强烈依赖于以H3 K27乙酰化为标志的染色质纤维结构的局部破坏。这也通过调节蛋白质介导的启动子-增强子环来显著影响基因座构型动力学。重要的是，这些模拟表明染色质动力学足够快，可以在几分钟内对所有可能的位点构象进行采样，从而在单细胞内产生广泛的动态变化。这种模拟和实验验证的结合提供了深入了解转录活性如何影响染色质结构和基因动力学。为了研究特定位点的动态三维结构，作者联合收割机了基于高分子物理的计算机建模方案和实验验证。他们的结果表明，染色质动力学足够快，可以在几分钟内对所有可能的位点构象进行采样，从而在单细胞内产生广泛的动态变化。
In living cells, the 3D structure of gene loci is dynamic, but this is not revealed by 3C and FISH experiments in fixed samples, leaving a notable gap in our understanding. To overcome these limitations, we applied the highly predictive heteromorphic polymer (HiP-HoP) model to determine chromatin fiber mobility at the Pax6 locus in three mouse cell lines with different transcription states. While transcriptional activity minimally affects movement of 40-kbp regions, we observed that motion of smaller 1-kbp regions depends strongly on local disruption to chromatin fiber structure marked by H3K27 acetylation. This also substantially influenced locus configuration dynamics by modulating protein-mediated promoter-enhancer loops. Importantly, these simulations indicate that chromatin dynamics are sufficiently fast to sample all possible locus conformations within minutes, generating wide dynamic variability within single cells. This combination of simulation and experimental validation provides insight into how transcriptional activity influences chromatin structure and gene dynamics. To study the dynamic 3D structure of specific loci, the authors combine a computer modeling scheme based on polymer physics with experimental validation. Their results indicate that chromatin dynamics are sufficiently fast to sample all possible locus conformations within minutes, generating wide dynamic variability within single cells.
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影响因子：
8.6
作者：
Eshghi I;Eaton JA;Zidovska A
通讯作者：
Zidovska A
影响因子：
8.8
作者：
Chiang, Michael;Michieletto, Davide;Chandra, Tamir
通讯作者：
Chandra, Tamir
DOI：
10.1126/science.aao3136
发表时间：
2018-03-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Gu B;Swigut T;Spencley A;Bauer MR;Chung M;Meyer T;Wysocka J
通讯作者：
Wysocka J
影响因子：
2.7
作者：
Brackley, C. A.
通讯作者：
Brackley, C. A.
影响因子：
4
作者：
Görisch, SM;Wachsmuth, M;Rippe, K
通讯作者：
Rippe, K