Institut Curie, Paris, France.
Bioessays. 2013 Sep;35(9):818-28. doi: 10.1002/bies.201300040. Epub 2013 Jul 5.
We discuss here a series of testable hypotheses concerning the role of chromosome folding into topologically associating domains (TADs). Several lines of evidence suggest that segmental packaging of chromosomal neighborhoods may underlie features of chromatin that span large domains, such as heterochromatin blocks, association with the nuclear lamina and replication timing. By defining which DNA elements preferentially contact each other, the segmentation of chromosomes into TADs may also underlie many properties of long-range transcriptional regulation. Several observations suggest that TADs can indeed provide a structural basis to regulatory landscapes, by controlling enhancer sharing and allocation. We also discuss how TADs may shape the evolution of chromosomes, by causing maintenance of synteny over large chromosomal segments. Finally we suggest a series of experiments to challenge these ideas and provide concrete examples illustrating how they could be practically applied.
我们在这里讨论了一系列关于染色体折叠成拓扑关联域（TAD）的作用的可测试假设。有几条证据表明，染色体局部区域的分段包装可能是跨越大域的染色质特征的基础，例如异染色质块、与核层的关联和复制时间。通过定义哪些 DNA 元件优先相互接触，将染色体分割成 TAD 也可能是长距离转录调控的许多特性的基础。有几个观察结果表明，TAD 确实可以通过控制增强子的共享和分配，为调控景观提供一个结构基础。我们还讨论了 TAD 如何通过在大的染色体片段上维持同线性来塑造染色体的进化。最后，我们提出了一系列实验来挑战这些观点，并提供了具体的例子来说明它们如何实际应用。
