Department of Neurobiology, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Genes (Basel). 2019 Jan 14;10(1):43. doi: 10.3390/genes10010043.
Enhancers are non-coding DNA elements that function in to regulate transcription from nearby genes. Through direct interactions with gene promoters, enhancers give rise to spatially and temporally precise gene expression profiles in distinct cell or tissue types. In the brain, the accurate regulation of these intricate expression programs across different neuronal classes gives rise to an incredible cellular and functional diversity. Newly developed technologies have recently allowed more accurate enhancer mapping and more sophisticated enhancer manipulation, producing rapid progress in our understanding of enhancer biology. Furthermore, identification of disease-linked genetic variation in enhancer regions has highlighted the potential influence of enhancers in brain health and disease. This review outlines the key role of enhancers as transcriptional regulators, reviews the current understanding of enhancer regulation in neuronal development, function and dysfunction and provides our thoughts on how enhancers can be targeted for technological and therapeutic goals.
增强子是发挥作用的非编码 DNA 元件，以调节附近基因的转录。通过与基因启动子的直接相互作用，增强子在不同的细胞或组织类型中产生空间和时间上精确的基因表达谱。在大脑中，不同神经元类群中这些复杂表达程序的精确调节产生了令人难以置信的细胞和功能多样性。最近新开发的技术允许更准确地绘制增强子图谱和更复杂的增强子操作，从而在增强子生物学的理解方面取得了快速进展。此外，增强子区域中与疾病相关的遗传变异的鉴定突出了增强子在大脑健康和疾病中的潜在影响。这篇综述概述了增强子作为转录调节剂的关键作用，回顾了目前对增强子在神经元发育、功能和功能障碍中的调控的理解，并就如何针对增强子设定技术和治疗目标提出了我们的想法。
