International Institute of Molecular and Cell Biology in Warsaw, 02-109 Warsaw, Poland.
Max Planck Institute for Heart and Lung Research, 61231 Bad Nauheim, Germany.
Int J Mol Sci. 2021 Apr 10;22(8):3914. doi: 10.3390/ijms22083914.
Precise control of gene expression is crucial to ensure proper development and biological functioning of an organism. Enhancers are non-coding DNA elements which play an essential role in regulating gene expression. They contain specific sequence motifs serving as binding sites for transcription factors which interact with the basal transcription machinery at their target genes. Heart development is regulated by intricate gene regulatory network ensuring precise spatiotemporal gene expression program. Mutations affecting enhancers have been shown to result in devastating forms of congenital heart defect. Therefore, identifying enhancers implicated in heart biology and understanding their mechanism is key to improve diagnosis and therapeutic options. Despite their crucial role, enhancers are poorly studied, mainly due to a lack of reliable way to identify them and determine their function. Nevertheless, recent technological advances have allowed rapid progress in enhancer discovery. Model organisms such as the zebrafish have contributed significant insights into the genetics of heart development through enabling functional analyses of genes and their regulatory elements in vivo. Here, we summarize the current state of knowledge on heart enhancers gained through studies in model organisms, discuss various approaches to discover and study their function, and finally suggest methods that could further advance research in this field.
精确控制基因表达对于确保生物的正常发育和生物学功能至关重要。增强子是一种非编码 DNA 元件，在调节基因表达方面发挥着重要作用。它们包含特定的序列基序，作为转录因子的结合位点，转录因子与它们的靶基因的基本转录机制相互作用。心脏发育受精细的基因调控网络调控，以确保精确的时空基因表达程序。已经表明，影响增强子的突变会导致严重形式的先天性心脏缺陷。因此，鉴定参与心脏生物学的增强子并了解其机制是改善诊断和治疗选择的关键。尽管它们具有至关重要的作用，但增强子的研究还很不完善，主要是因为缺乏可靠的方法来识别它们并确定它们的功能。然而，最近的技术进步使得增强子的发现取得了快速进展。斑马鱼等模式生物通过在体内对基因及其调控元件进行功能分析，为心脏发育的遗传学研究做出了重大贡献。在这里，我们总结了通过模式生物研究获得的关于心脏增强子的最新知识，讨论了发现和研究其功能的各种方法，并最终提出了可能进一步推动该领域研究的方法。
