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果蝇胚胎中神经源性基因表达的调控密码。

A regulatory code for neurogenic gene expression in the Drosophila embryo.

作者信息

Markstein Michele, Zinzen Robert, Markstein Peter, Yee Ka-Ping, Erives Albert, Stathopoulos Angela, Levine Michael

机构信息

Department of Molecular and Cellular Biology, Division of Genetics and Development, 401 Barker Hall, University of California, Berkeley, CA 94720, USA.

出版信息

Development. 2004 May;131(10):2387-94. doi: 10.1242/dev.01124.

Abstract

Bioinformatics methods have identified enhancers that mediate restricted expression in the Drosophila embryo. However, only a small fraction of the predicted enhancers actually work when tested in vivo. In the present study, co-regulated neurogenic enhancers that are activated by intermediate levels of the Dorsal regulatory gradient are shown to contain several shared sequence motifs. These motifs permitted the identification of new neurogenic enhancers with high precision: five out of seven predicted enhancers direct restricted expression within ventral regions of the neurogenic ectoderm. Mutations in some of the shared motifs disrupt enhancer function, and evidence is presented that the Twist and Su(H) regulatory proteins are essential for the specification of the ventral neurogenic ectoderm prior to gastrulation. The regulatory model of neurogenic gene expression defined in this study permitted the identification of a neurogenic enhancer in the distant Anopheles genome. We discuss the prospects for deciphering regulatory codes that link primary DNA sequence information with predicted patterns of gene expression.

摘要

生物信息学方法已经鉴定出了在果蝇胚胎中介导特异性表达的增强子。然而,在体内测试时,只有一小部分预测的增强子实际发挥作用。在本研究中,由中等水平的背侧调节梯度激活的共同调节的神经源性增强子显示含有几个共享的序列基序。这些基序使得能够高精度地鉴定出新的神经源性增强子:七个预测的增强子中有五个在神经外胚层的腹侧区域指导特异性表达。一些共享基序中的突变会破坏增强子功能,并且有证据表明,在原肠胚形成之前,Twist和Su(H)调节蛋白对于腹侧神经外胚层的特化至关重要。本研究中定义的神经源性基因表达调节模型使得能够在远缘的按蚊基因组中鉴定出一个神经源性增强子。我们讨论了解读将初级DNA序列信息与预测的基因表达模式联系起来的调节密码的前景。

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