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发展与疾病中调控景观动态的进化观点。

An evolutionary perspective of regulatory landscape dynamics in development and disease.

机构信息

Centro Andaluz de Biología del Desarrollo (CABD), Consejo Superior de Investigaciones Científicas/Universidad Pablo de Olavide/Junta de Andalucía, Sevilla, Spain.

出版信息

Curr Opin Cell Biol. 2018 Dec;55:24-29. doi: 10.1016/j.ceb.2018.06.009. Epub 2018 Jul 11.

DOI:10.1016/j.ceb.2018.06.009
PMID:30006052
Abstract

The organization of animal genomes into topologically associating domains (TADs) provides a structural scaffold in which cis-regulatory elements (CREs) operate on their target genes. Determining the position of CREs and genes relative to TADs has become instrumental to trace gene expression changes during evolution and in diseases. Here we will review recent studies and discuss TADs as structural units with respect to their conservation and stability during genome reorganization. Furthermore, we describe how TAD restructuring contributed to morphological novelties during evolution but also their deleterious effects associated with disease. Despite considering TADs as structural units, the nested and dynamic scaffold within TADs contributes to tissue-specific gene expression, implying that such changes can also account for gene expression differences during evolution.

摘要

动物基因组组织成拓扑关联域(TAD)为顺式调控元件(CREs)在其靶基因上发挥作用提供了一个结构支架。确定 CREs 和基因相对于 TAD 的位置对于追踪进化和疾病过程中的基因表达变化至关重要。在这里,我们将回顾最近的研究,并讨论 TAD 作为结构单元,就其在基因组重排过程中的保守性和稳定性而言。此外,我们还描述了 TAD 结构重排如何在进化过程中导致形态新颖性,但也描述了它们与疾病相关的有害影响。尽管将 TAD 视为结构单元,但 TAD 内嵌套和动态的支架有助于组织特异性基因表达,这意味着这种变化也可以解释进化过程中基因表达的差异。

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