TAD disruption as oncogenic driver.
TAD disruption as oncogenic driver.
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TAD 干扰是致癌驱动因素。
DOI：
10.1016/j.gde.2016.03.008
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发表时间：
2016-02
影响因子：
4
通讯作者：
Dekker J
中科院分区：
文献类型：
--
作者：
Valton AL;Dekker J
拓扑关联结构域 (TAD) 在进化过程中是保守的，在指导和限制基因表达的远程调控中发挥作用。 TAD 边界的破坏通过将基因暴露于不适当的调控元件而导致异常的基因表达。最近的研究表明，TAD 破坏经常存在于癌细胞中，并通过两种机制促进肿瘤发生。一种机制通过删除或突变 TAD 边界来局部破坏域，从而导致两个相邻 TAD 的融合。另一种机制涉及基因组重排，可以分解 TAD 并创建新的 TAD，而不直接影响 TAD 边界。因此，了解 TAD 形成和控制长程染色质相互作用的机制不仅可以深入了解基因调控的一般机制，而且还将揭示癌症基因组中的基因组重排和突变如何导致癌基因和肿瘤抑制因子的错误调控。
Topologically Associating Domains (TADs) are conserved during evolution and play roles in guiding and constraining long-range regulation of gene expression. Disruption of TAD boundaries results in aberrant gene expression by exposing genes to inappropriate regulatory elements. Recent studies have shown that TAD disruption is often found in cancer cells and contributes to oncogenesis through two mechanisms. One mechanism locally disrupts domains by deleting or mutating a TAD boundary leading to fusion of the two adjacent TADs. The other mechanism involves genomic rearrangements that break up TADs and creates new ones without directly affecting TAD boundaries. Understanding the mechanisms by which TADs form and control long-range chromatin interactions will therefore not only provide insights into the mechanism of gene regulation in general, but will also reveal how genomic rearrangements and mutations in cancer genomes can lead to misregulation of oncogenes and tumor suppressors.