Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines.
Replication fork polarity gradients revealed by megabase-sized U-shaped replication timing domains in human cell lines.
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DOI：
10.1371/journal.pcbi.1002443
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发表时间：
2012
影响因子：
4.3
通讯作者：
Arneodo A
中科院分区：
文献类型：
--
作者：
Baker A;Audit B;Chen CL;Moindrot B;Leleu A;Guilbaud G;Rappailles A;Vaillant C;Goldar A;Mongelard F;d'Aubenton-Carafa Y;Hyrien O;Thermes C;Arneodo A
在高等真核生物中，不同细胞类型的复制程序规范仍有待充分理解。我们显示了7个人类细胞系，约有一半的基因组被划分在域中，显示出一个特征性的U形复制时序分布，早期起始区在边界和晚期复制中心。不同细胞系的U-结构域之间观察到显著的重叠，并且还与表现出N形核苷酸组成偏斜的种系复制结构域。从示范，平均叉极性直接反映了由两个组成的偏斜和衍生物的复制时序配置文件，我们认为，这个衍生物显示一个N-形状的U-域的事实，维持存在的大规模梯度的复制叉极性在体细胞和生殖细胞。染色质相互作用（Hi-C）和染色质标记数据的分析表明，U-结构域对应于高阶染色质结构单元。我们讨论了可能的模型复制起点激活内U/N-域。将基因组划分为复制U/N结构域提供了关于人类基因组中复制程序组织的新见解。人类细胞中的DNA复制需要沿着数千个复制机器的基因组平行进行。不同发育阶段的遗传遗传的全面知识依赖于阐明在细胞周期的DNA合成阶段的整个持续时间内调节这些机器的位置和进展的机制。在这里，我们确定在多种人类细胞类型中存在一种新型的兆碱基大小的复制结构域，其中复制机制的平均方向以线性方式变化。这些领域揭示了在7体细胞类型的复制定时配置文件中的U形图案，以及由N形图案的DNA组成的不对称性配置文件中，反映了存在的复制相关的突变不对称性的种系。因此，这些结构域对应于跨细胞类型和进化过程中的稳健复制模式。使用有关两个细胞系中远端染色质片段相互作用频率的全基因组数据，我们发现这些U/N复制结构域显着对应于染色质纤维的自相互作用折叠单元。
In higher eukaryotes, replication program specification in different cell types remains to be fully understood. We show for seven human cell lines that about half of the genome is divided in domains that display a characteristic U-shaped replication timing profile with early initiation zones at borders and late replication at centers. Significant overlap is observed between U-domains of different cell lines and also with germline replication domains exhibiting a N-shaped nucleotide compositional skew. From the demonstration that the average fork polarity is directly reflected by both the compositional skew and the derivative of the replication timing profile, we argue that the fact that this derivative displays a N-shape in U-domains sustains the existence of large-scale gradients of replication fork polarity in somatic and germline cells. Analysis of chromatin interaction (Hi-C) and chromatin marker data reveals that U-domains correspond to high-order chromatin structural units. We discuss possible models for replication origin activation within U/N-domains. The compartmentalization of the genome into replication U/N-domains provides new insights on the organization of the replication program in the human genome. DNA replication in human cells requires the parallel progression along the genome of thousands of replication machineries. Comprehensive knowledge of genetic inheritance at different development stages relies on elucidating the mechanisms that regulate the location and progression of these machineries throughout the duration of the DNA synthetic phase of the cell cycle. Here, we determine in multiple human cell types the existence of a new type of megabase-sized replication domains across which the average orientation of the replication machinery changes in a linear manner. These domains are revealed in 7 somatic cell types by a U-shaped pattern in the replication timing profiles as well as by N-shaped patterns in the DNA compositional asymmetry profile reflecting the existence of a replication-associated mutational asymmetry in the germline. These domains therefore correspond to a robust mode of replication across cell types and during evolution. Using genome-wide data on the frequency of interaction of distant chromatin segments in two cell lines, we find that these U/N-replication domains remarkably correspond to self-interacting folding units of the chromatin fiber.
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影响因子：
8.6
作者：
Audit, B.;Nicolay, S.;Arneodo, A.
通讯作者：
Arneodo, A.
影响因子：
8.6
作者：
Brodie, EB;Nicolay, S;Arneodo, A
通讯作者：
Arneodo, A
影响因子：
64.5
作者：
Gilbert, N;Boyle, S;Bickmore, WA
通讯作者：
Bickmore, WA
影响因子：
14.9
作者：
Audit B;Zaghloul L;Vaillant C;Chevereau G;d'Aubenton-Carafa Y;Thermes C;Arneodo A
通讯作者：
Arneodo A
影响因子：
7
作者：
Farkash-Amar, Shlomit;Lipson, Doron;Simon, Itamar
通讯作者：
Simon, Itamar