Functional genomic approaches to elucidate the role of enhancers during development.

IF 7.9 Q1 Medicine Wiley Interdisciplinary Reviews-Systems Biology and Medicine Pub Date : 2020-03-01 Epub Date: 2019-12-05 DOI:10.1002/wsbm.1467
Genevieve E Ryan, Emma K Farley
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引用次数: 22

Abstract

Successful development depends on the precise tissue-specific regulation of genes by enhancers, genetic elements that act as switches to control when and where genes are expressed. Because enhancers are critical for development, and the majority of disease-associated mutations reside within enhancers, it is essential to understand which sequences within enhancers are important for function. Advances in sequencing technology have enabled the rapid generation of genomic data that predict putative active enhancers, but functionally validating these sequences at scale remains a fundamental challenge. Herein, we discuss the power of genome-wide strategies used to identify candidate enhancers, and also highlight limitations and misconceptions that have arisen from these data. We discuss the use of massively parallel reporter assays to test enhancers for function at scale. We also review recent advances in our ability to study gene regulation during development, including CRISPR-based tools to manipulate genomes and single-cell transcriptomics to finely map gene expression. Finally, we look ahead to a synthesis of complementary genomic approaches that will advance our understanding of enhancer function during development. This article is categorized under: Physiology > Mammalian Physiology in Health and Disease Developmental Biology > Developmental Processes in Health and Disease Laboratory Methods and Technologies > Genetic/Genomic Methods.

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功能基因组学方法阐明增强子在发育过程中的作用。
成功的发育依赖于增强子对基因的精确组织特异性调控,增强子是作为开关的遗传元素,控制基因何时何地表达。由于增强子对发育至关重要,并且大多数疾病相关突变都存在于增强子中,因此了解增强子中的哪些序列对功能重要至关重要。测序技术的进步使得能够快速生成预测活性增强子的基因组数据,但是大规模地对这些序列进行功能验证仍然是一个根本性的挑战。在此,我们讨论了用于识别候选增强子的全基因组策略的力量,并强调了从这些数据中产生的局限性和误解。我们讨论了大规模并行报告分析的使用,以大规模测试功能增强子。我们还回顾了我们在发育过程中研究基因调控能力的最新进展,包括基于crispr的工具来操纵基因组和单细胞转录组学来精细地绘制基因表达。最后,我们展望了互补基因组方法的综合,这将促进我们对发育过程中增强子功能的理解。本文分类为:生理学b>健康与疾病中的哺乳动物生理学发育生物学>健康与疾病中的发育过程实验室方法与技术>遗传/基因组方法。
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来源期刊
CiteScore
18.40
自引率
0.00%
发文量
0
审稿时长
>12 weeks
期刊介绍: Journal Name:Wiley Interdisciplinary Reviews-Systems Biology and Medicine Focus: Strong interdisciplinary focus Serves as an encyclopedic reference for systems biology research Conceptual Framework: Systems biology asserts the study of organisms as hierarchical systems or networks Individual biological components interact in complex ways within these systems Article Coverage: Discusses biology, methods, and models Spans systems from a few molecules to whole species Topical Coverage: Developmental Biology Physiology Biological Mechanisms Models of Systems, Properties, and Processes Laboratory Methods and Technologies Translational, Genomic, and Systems Medicine
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