Nuclear biology: what's been most surprising?
Nuclear biology: what's been most surprising?
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DOI：
10.1016/j.cell.2013.02.041
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发表时间：
2013-03-14
期刊：
影响因子：
64.5
通讯作者：
Pikaard C
中科院分区：
文献类型：
--
作者：
Dekker J;Wysocka J;Mattaj I;Lieberman Aiden E;Pikaard C
人类基因组的调控潜力比一些人预期的要丰富得多。通过极其精细的注释，我们现在意识到每个基因都发现自己在一个非常拥挤的细胞核中被大量潜在的调控元件包围。鉴于许多调控元件通过直接的物理相互作用来控制基因，我们可以想象，这可能会造成一种潜在的危险情况，即基因因偶然遇到不适当的元件而受到错误调节。因此，核组织领域的一个主要问题是细胞如何确保基因只对正确的调控元件做出反应，而忽略数十万个其他元件？最近的工作揭示了一种令人惊讶的简单策略，将基因仅与某些调控元件相匹配，其中涉及细胞核内染色体的空间组织和折叠。在果蝇、小鼠和人类的细胞核中，染色体在空间上是分开的。利用 5C 和 Hi-C 技术，研究表明染色体形成拓扑关联域 (TAD) 串，每个拓扑关联域的大小为数百 Kb，但在空间上与相邻的 TAD 隔离。因此，给定的基因生活在一个相对较小的邻域中，在那里它只遇到基因组的一小部分，因此只能与少量的调控元件配合。未来的研究无疑将揭示 TAD 是如何建立的，以及它们如何将基因与错误的人群隔离开来。
The regulatory potential of the human genome is much richer than some had anticipated. With greatly refined annotations, we now realize that each gene finds itself surrounded by a huge number of potentially regulatory elements in a very crowded nucleus. Given that many regulatory elements control genes through direct physical interaction, one can imagine that this could create a potentially risky situation in which genes get misregulated by chance encounters with inappropriate elements. So, a major question in the field of nuclear organization is how do cells ensure that genes only respond to the right regulatory elements while ignoring the hundreds of thousands of others? Recent work has revealed a surprisingly simple strategy for matching genes to only some regulatory elements, which involves the spatial organization and folding of chromosomes inside the nucleus. In Drosophila, mouse, and human nuclei, chromosomes are spatially compartmentalized. Using 5C and Hi-C technologies, it has been shown that chromosomes form strings of topologically associating domains (TADs) that are each hundreds of Kb in size but are spatially insulated from neighboring TADs. As a result, a given gene lives in a relatively small neighborhood where it encounters only a small section of the genome and thus can partner with only a small number of regulatory elements. Future studies will no doubt unveil how TADs are established and how they insulate genes from the wrong crowd.