Understanding fundamental principles of enhancer biology at a model locus: Analysing the structure and function of an enhancer cluster at the a-globin locus.
Understanding fundamental principles of enhancer biology at a model locus: Analysing the structure and function of an enhancer cluster at the a-globin locus.
复制标题
了解模型基因座增强子生物学的基本原理：分析 a-珠蛋白基因座增强子簇的结构和功能。
DOI：
10.1002/bies.202300047
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Kassouf M
中科院分区：
文献类型：
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作者：
Kassouf M
尽管基因组数据的积累不断增加，但个体基因在发育、谱系特化和分化过程中如何开启的基本问题尚未得到完全回答。人们普遍认为，这涉及至少三个基本调控元件之间的相互作用：增强子，启动子和绝缘子。增强子含有转录因子结合位点，其被细胞命运决定期间表达的转录因子（TF）和辅因子结合，并至少部分地通过其表观遗传修饰维持强加的激活模式。这些信息通常通过紧密的物理接近从增强子转移到其同源启动子，以形成含有高浓度TF和辅因子的“转录中心”。这些转录激活阶段的机制尚未完全解释。本文综述了增强子和启动子在分化过程中是如何被激活的，以及多个增强子是如何共同调节基因表达的。我们说明了目前理解的哺乳动物增强子如何工作的原则，以及它们如何在增强子病中使用红细胞生成过程中α珠蛋白基因簇的表达作为模型受到干扰。
Despite ever‐increasing accumulation of genomic data, the fundamental question of how individual genes are switched on during development, lineage‐specification and differentiation is not fully answered. It is widely accepted that this involves the interaction between at least three fundamental regulatory elements: enhancers, promoters and insulators. Enhancers contain transcription factor binding sites which are bound by transcription factors (TFs) and co‐factors expressed during cell fate decisions and maintain imposed patterns of activation, at least in part, via their epigenetic modification. This information is transferred from enhancers to their cognate promoters often by coming into close physical proximity to form a ‘transcriptional hub’ containing a high concentration of TFs and co‐factors. The mechanisms underlying these stages of transcriptional activation are not fully explained. This review focuses on how enhancers and promoters are activated during differentiation and how multiple enhancers work together to regulate gene expression. We illustrate the currently understood principles of how mammalian enhancers work and how they may be perturbed in enhanceropathies using expression of the α‐globin gene cluster during erythropoiesis, as a model.