Replication dynamics identifies the folding principles of the inactive X chromosome.
Replication dynamics identifies the folding principles of the inactive X chromosome.
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DOI：
10.1038/s41594-023-01052-1
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发表时间：
2023-08
影响因子：
16.8
通讯作者：
Hiratani, Ichiro
中科院分区：
文献类型：
--
作者：
Poonperm, Rawin;Ichihara, Saya;Miura, Hisashi;Tanigawa, Akie;Nagao, Koji;Obuse, Chikashi;Sado, Takashi;Hiratani, Ichiro
染色体范围内的晚期复制是失活 X 染色体 (Xi) 的一个神秘标志。它是如何建立的以及它代表什么仍然不清楚。通过单细胞DNA复制测序，我们发现整个Xi在X染色体失活（XCI）期间的S期晚期进行重组，快速、均匀地复制，反映了4C-seq揭示的其相对均匀的结构。尽管存在这种一致性，但只有 Xi 的一个子集在 SmcHD1 突变细胞中较早复制。在突变体中，这些结构域从 Xi 核心突出，相互接触并转录重新激活。 4C-seq表明它们甚至在XCI之前就构成了Xi的最外层，并且富含逃逸基因。我们认为，这种默认定位构成了缺乏 Xi 结合蛋白 SmcHD1 或表现出 XCI 逃逸的细胞中固有异染色质不稳定性的基础。这些观察结果强调了 3D 基因组组织对于异染色质稳定性和基因调控的重要性。染色体范围内的晚期复制是失活 X 的一个神秘标志。在这里，作者结合了 scRepli-seq 和 4C-seq 来揭示其分层的 3D 结构，这可以解释异染色质稳定性的局部差异。
Chromosome-wide late replication is an enigmatic hallmark of the inactive X chromosome (Xi). How it is established and what it represents remains obscure. By single-cell DNA replication sequencing, here we show that the entire Xi is reorganized to replicate rapidly and uniformly in late S-phase during X-chromosome inactivation (XCI), reflecting its relatively uniform structure revealed by 4C-seq. Despite this uniformity, only a subset of the Xi became earlier replicating in SmcHD1-mutant cells. In the mutant, these domains protruded out of the Xi core, contacted each other and became transcriptionally reactivated. 4C-seq suggested that they constituted the outermost layer of the Xi even before XCI and were rich in escape genes. We propose that this default positioning forms the basis for their inherent heterochromatin instability in cells lacking the Xi-binding protein SmcHD1 or exhibiting XCI escape. These observations underscore the importance of 3D genome organization for heterochromatin stability and gene regulation. Chromosome-wide late replication is an enigmatic hallmark of the inactive X. Here, the authors combined scRepli-seq and 4C-seq to reveal its layered 3D architecture, which could explain local differences in heterochromatin stability.
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影响因子：
1.5
作者：
Disteche CM;Berletch JB
通讯作者：
Berletch JB
影响因子：
16.6
作者：
Casas-Delucchi, Corella S.;Brero, Alessandro;Cardoso, M. Cristina
通讯作者：
Cardoso, M. Cristina
影响因子：
64.8
作者：
Dixon JR;Jung I;Selvaraj S;Shen Y;Antosiewicz-Bourget JE;Lee AY;Ye Z;Kim A;Rajagopal N;Xie W;Diao Y;Liang J;Zhao H;Lobanenkov VV;Ecker JR;Thomson JA;Ren B
通讯作者：
Ren B
DOI：
10.1083/jcb.7.3.455
发表时间：
1960-06
期刊：
The Journal of biophysical and biochemical cytology
影响因子：
--
作者：
TAYLOR, J H
通讯作者：
TAYLOR, J H
影响因子：
16.6
作者：
Dileep V;Gilbert DM
通讯作者：
Gilbert DM