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PDP1是一种在中胚层、内胚层和外胚层发育过程中表达的新型果蝇PAR结构域bZIP转录因子,是体肌基因的转录调节因子。

PDP1, a novel Drosophila PAR domain bZIP transcription factor expressed in developing mesoderm, endoderm and ectoderm, is a transcriptional regulator of somatic muscle genes.

作者信息

Lin S C, Lin M H, Horváth P, Reddy K L, Storti R V

机构信息

Department of Biochemistry and Molecular Biology M/C536, University of Illinois College of Medicine, Chicago 60612, USA.

出版信息

Development. 1997 Nov;124(22):4685-96. doi: 10.1242/dev.124.22.4685.

Abstract

In vertebrates, transcriptional control of skeletal muscle genes during differentiation is regulated by enhancers that direct the combinatorial binding and/or interaction of MEF2 and the bHLH MyoD family of myogenic factors. We have shown that Drosophila MEF2 plays a role similar to its vertebrate counterpart in the regulation of the Tropomyosin I gene in the development of Drosophila somatic muscles, however, unlike vertebrates, Drosophila MEF2 interacts with a muscle activator region that does not have binding sites for myogenic bHLH-like factors or any other known Drosophila transcription factors. We describe here the isolation and characterization of a component of the muscle activator region that we have named PDP1 (PAR domain protein 1). PDP1 is a novel transcription factor that is highly homologous to the PAR subfamily of mammalian bZIP transcription factors HLF, DBP and VBP/TEF. This is the first member of the PAR subfamily of bZIP transcription factors to be identified in Drosophila. We show that PDP1 is involved in regulating expression of the Tropomyosin I gene in somatic body-wall and pharyngeal muscles by binding to DNA sequences within the muscle activator that are required for activator function. Mutations that eliminate PDP1 binding eliminate muscle activator function and severely reduce expression of a muscle activator plus MEF2 mini-enhancer. These and previous results suggest that PDP1 may function as part of a larger protein/DNA complex that interacts with MEF2 to regulate transcription of Drosophila muscle genes. Furthermore, in addition to being expressed in the mesoderm that gives rise to the somatic muscles, PDP1 is also expressed in the mesodermal fat body, the developing midgut endoderm, the hindgut and Malpighian tubules, and the epidermis and central nervous system, suggesting that PDP1 is also involved in the terminal differentiation of these tissues.

摘要

在脊椎动物中,骨骼肌基因在分化过程中的转录调控由增强子介导,这些增强子指导MEF2与肌源性因子的bHLH MyoD家族进行组合结合和/或相互作用。我们已经表明,果蝇MEF2在果蝇体壁肌肉发育过程中对原肌球蛋白I基因的调控中发挥着与其脊椎动物对应物相似的作用,然而,与脊椎动物不同的是,果蝇MEF2与一个肌肉激活区域相互作用,该区域没有肌源性bHLH样因子或任何其他已知果蝇转录因子的结合位点。我们在此描述了一个肌肉激活区域成分的分离和特性,我们将其命名为PDP1(PAR结构域蛋白1)。PDP1是一种新型转录因子,与哺乳动物bZIP转录因子HLF、DBP和VBP/TEF的PAR亚家族高度同源。这是在果蝇中鉴定出的bZIP转录因子PAR亚家族的首个成员。我们表明,PDP1通过与激活功能所需的肌肉激活剂内的DNA序列结合,参与调节体壁和咽肌中原肌球蛋白I基因的表达。消除PDP1结合的突变会消除肌肉激活剂功能,并严重降低肌肉激活剂加MEF2微型增强子的表达。这些以及先前的结果表明,PDP1可能作为一个更大的蛋白质/DNA复合物的一部分发挥作用,该复合物与MEF2相互作用以调节果蝇肌肉基因的转录。此外,除了在产生体壁肌肉的中胚层中表达外,PDP1还在中胚层脂肪体、发育中的中肠内胚层、后肠和马氏管以及表皮和中枢神经系统中表达,这表明PDP1也参与这些组织的终末分化。

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