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Hox转录因子:基因表达多步骤调节因子概述

Hox transcription factors: an overview of multi-step regulators of gene expression.

作者信息

Carnesecchi Julie, Pinto Pedro B, Lohmann Ingrid

机构信息

Heidelberg University, Centre for Organismal Studies (COS) Heidelberg, Department of Developmental Biology, Heidelberg, Germany.

出版信息

Int J Dev Biol. 2018;62(11-12):723-732. doi: 10.1387/ijdb.180294il.

Abstract

Hox transcription factors (TFs) function as key determinants in the specification of cell fates during development. They do so by triggering entire morphogenetic cascades through the activation of specific target genes. In contrast to their fundamental role in development, the molecular mechanisms employed by Hox TFs are still poorly understood. In recent years, a new picture has emerged regarding the function of Hox proteins in gene regulation. Initial studies have primarily focused on understanding how Hox TFs recognize and bind specific enhancers to activate defined Hox targets. However, genome-wide studies on the interactions and dynamics of Hox proteins have revealed a more elaborate function of the Hox factors. It is now known that Hox proteins are involved in several steps of gene expression with potential regulatory functions in the modification of the chromatin landscape and its accessibility, recognition and activation of specific cis-regulatory modules, assembly and activation of promoter transcription complexes and mRNA processing. In the coming years, the characterization of the molecular activity of Hox TFs in these mechanisms will greatly contribute to our general understanding of Hox activity.

摘要

Hox转录因子(TFs)在发育过程中作为细胞命运特化的关键决定因素发挥作用。它们通过激活特定靶基因触发整个形态发生级联反应来实现这一点。与它们在发育中的基本作用形成对比的是,Hox转录因子所采用的分子机制仍知之甚少。近年来,关于Hox蛋白在基因调控中的功能出现了一幅新的图景。最初的研究主要集中在理解Hox转录因子如何识别和结合特定增强子以激活特定的Hox靶标。然而,关于Hox蛋白相互作用和动态变化的全基因组研究揭示了Hox因子更为复杂的功能。现在已知Hox蛋白参与基因表达的多个步骤,在染色质景观及其可及性的修饰、特定顺式调控模块的识别和激活、启动子转录复合物的组装和激活以及mRNA加工方面具有潜在的调控功能。在未来几年,对Hox转录因子在这些机制中的分子活性的表征将极大地有助于我们对Hox活性的总体理解。

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