Breaking enhancers to gain insights into developmental defects.
Breaking enhancers to gain insights into developmental defects.
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作者：
Armendariz DA;Sundarrajan A;Hon GC
尽管突破性的遗传研究已经确定了数千种发育性疾病的风险变异，但这些变异如何导致分子和细胞表型仍然是知识上的空白。许多这些变体是非编码的，发生在增强子上，增强子在发育过程中协调关键的调控程序。普遍的范式是，非编码变异改变增强子的活性，影响基因表达程序，并最终导致疾病风险。进展的一个关键障碍是大规模的非编码变异的系统功能表征，特别是因为增强子的活性对细胞类型和发育阶段具有高度特异性。在这里，我们回顾了增强子在发育性疾病中的基础研究，以及目前用于大规模表征发育增强子及其变异的基因组方法。在未来十年，我们期望系统的增强子扰动研究将非编码变异与分子机制、细胞状态变化和疾病表型联系起来。
Despite ground-breaking genetic studies that have identified thousands of risk variants for developmental diseases, how these variants lead to molecular and cellular phenotypes remains a gap in knowledge. Many of these variants are non-coding and occur at enhancers, which orchestrate key regulatory programs during development. The prevailing paradigm is that non-coding variants alter the activity of enhancers, impacting gene expression programs, and ultimately contributing to disease risk. A key obstacle to progress is the systematic functional characterization of non-coding variants at scale, especially since enhancer activity is highly specific to cell type and developmental stage. Here, we review the foundational studies of enhancers in developmental disease and current genomic approaches to functionally characterize developmental enhancers and their variants at scale. In the coming decade, we anticipate systematic enhancer perturbation studies to link non-coding variants to molecular mechanisms, changes in cell state, and disease phenotypes.
影响因子：
14.9
作者：
Morbitzer R;Elsaesser J;Hausner J;Lahaye T
通讯作者：
Lahaye T