Department of Biomedical Sciences, The University of North Dakota, USA; Department of Genetics, School of Medicine, Yale University, 830, West Campus Drive, West Haven, 06516, USA.
Department of Biology, The University of North Dakota, USA.
Dev Biol. 2021 Sep;477:284-292. doi: 10.1016/j.ydbio.2021.06.002. Epub 2021 Jun 6.
Homeotic genes (Hox genes) are homeodomain-transcription factors involved in conferring segmental identity along the anterior-posterior body axis. Molecular characterization of HOX protein function raises some interesting questions regarding the source of the binding specificity of the HOX proteins. How do HOX proteins regulate common and unique target specificity across space and time? This review attempts to summarize and interpret findings in this area, largely focused on results from in vitro and in vivo studies in Drosophila and mouse systems. Recent studies related to HOX protein binding specificity compel us to reconsider some of our current models for transcription factor-DNA interactions. It is crucial to study transcription factor binding by incorporating components of more complex, multi-protein interactions in concert with small changes in binding motifs that can significantly impact DNA binding specificity and subsequent alterations in gene expression. To incorporate the multiple elements that can determine HOX protein binding specificity, we propose a more integrative Cooperative Binding model.
同源异形基因(Hox 基因)是同源域转录因子,参与沿身体前后轴赋予节段性同一性。HOX 蛋白功能的分子特征提出了一些关于 HOX 蛋白结合特异性来源的有趣问题。HOX 蛋白如何在空间和时间上调节共同和独特的靶标特异性?本综述试图总结和解释这一领域的发现,主要集中在果蝇和小鼠系统的体外和体内研究结果上。与 HOX 蛋白结合特异性相关的最新研究迫使我们重新考虑我们当前的一些转录因子-DNA 相互作用模型。通过将更复杂的多蛋白相互作用的成分与结合基序的微小变化结合起来,研究转录因子的结合对于显著影响 DNA 结合特异性并随后改变基因表达至关重要。为了纳入多个决定 HOX 蛋白结合特异性的因素,我们提出了一个更具综合性的协同结合模型。