Identification of shared transcriptional targets for the proneural bHLH factors Xath5 and XNeuroD

Identification of shared transcriptional targets for the proneural bHLH factors Xath5 and XNeuroD
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DOI:
10.1016/j.ydbio.2005.06.033
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发表时间:
2005-09-15
影响因子:
2.7
通讯作者:
Vetter, ML
Vetter, ML
中科院分区:
生物学3区
文献类型:
--
作者:
Logan, MA;Steele, MR;Vetter, ML

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原神经性碱性螺旋-环-螺旋转录因子是多种物种神经元分化的关键正向调节因子,对不同亚型神经元的正确分化是必需的。虽然bHLH因子在神经发育过程中表现出一些独特的功能,但它们有共同的能力来调节神经元的分化,可能是通过靶向重叠的基因集。为了评估这一点,我们在外胚层动物帽子组织中进行了筛选,以确定两个与非洲爪哇ATO相关的bHLH因子Xath5和X-Neurd共享的直接转录靶点。在这个筛选中发现的候选靶基因包括几个转录调控基因(Xebf2、Xebf3、XETOR和NKL)、一个RNA结合蛋白(E1rC)、一个细胞周期成分(Xgadd45 Gamma)和几个新基因。Xath5或XNeuroD的过表达诱导了这些候选靶基因的体内异位表达。相反,阻断与ATO相关的bHLH活性可阻止内源性神经系统表达这些基因。因此,我们已经确定了一组基因,它们可以被多种ATO相关的bHLH因子调控,并可能作为bHLH介导的原神经分化的关键效应因子。(C)2005 Elsevier Inc.保留所有权利。
Proneural basic helix-loop-helix (bHLH) transcription factors are critical positive regulators of neuronal differentiation in a variety of species and are required for proper differentiation of various subtypes of neurons. Although bHLH factors demonstrate some unique functions during neural development, they share the ability to regulate neuronal differentiation, potentially by targeting overlapping sets of genes. To assess this, we performed a screen in ectoderm animal cap tissue to identify direct transcriptional targets shared by two Xenopus ato-related bHLH factors, Xath5 and X-NeuroD. Candidate target genes identified in this screen include several transcriptional regulators (Xebf2, Xebf3, XETOR and NKL), an RNA binding protein (e1rC), a cell cycle component (Xgadd45 gamma) and several novel genes. Overexpression of either Xath5 or XNeuroD induced ectopic in vivo expression of these candidate target genes. Conversely, blocking ato-related bHLH activity prevented endogenous nervous system expression of these genes. Therefore, we have identified a set of genes that can be regulated by multiple ato-related bHLH factors and may function as critical effectors of proneural bHLH-mediated differentiation. (c) 2005 Elsevier Inc. All rights reserved.