Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers.
Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers.
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DOI：
10.1101/gad.14.14.1750
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发表时间：
2000-07
影响因子：
10.5
通讯作者：
Lingyang Zhu;J. Wilken;N. Phillips;U. Narendra;G. Chan;S. M. Stratton;S. Kent;M. Weiss
中科院分区：
文献类型：
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作者：
Lingyang Zhu;J. Wilken;N. Phillips;U. Narendra;G. Chan;S. M. Stratton;S. Kent;M. Weiss
性别决定受到多种途径的调节。尽管上游信号各不相同，但富含半胱氨酸的 DNA 结合域（DM 基序）在果蝇 (Doublesex) 和秀丽隐杆线虫 (MAB-3) 的下游转录因子中是保守的。脊椎动物的 DM 基因同样已被鉴定，并且值得注意的是，它们与人类性别逆转（46，XY 性腺发育不全）有关。在这里，我们证明了 Doublesex 结构域的结构包含一个新颖的锌模块和无序的尾部。该模块由相互缠绕的 CCHC 和 HCCC Zn(2+) 结合位点组成；尾部起到新生识别α螺旋的作用。 Zn(2+) 结合位点或尾部的突变可导致双性表型。该基序结合在 DNA 小沟中，没有尖锐的 DNA 弯曲。这些分子特征在锌指和锌模块中不常见，是整合性别和组织特异性信号的果蝇增强子组织的基础。该结构为分析影响性二态性和求偶行为的 DM 突变提供了基础。
Sex determination is regulated by diverse pathways. Although upstream signals vary, a cysteine-rich DNA-binding domain (the DM motif) is conserved within downstream transcription factors of Drosophila melanogaster (Doublesex) and Caenorhabditis elegans (MAB-3). Vertebrate DM genes have likewise been identified and, remarkably, are associated with human sex reversal (46, XY gonadal dysgenesis). Here we demonstrate that the structure of the Doublesex domain contains a novel zinc module and disordered tail. The module consists of intertwined CCHC and HCCC Zn(2+)-binding sites; the tail functions as a nascent recognition alpha-helix. Mutations in either Zn(2+)-binding site or tail can lead to an intersex phenotype. The motif binds in the DNA minor groove without sharp DNA bending. These molecular features, unusual among zinc fingers and zinc modules, underlie the organization of a Drosophila enhancer that integrates sex- and tissue-specific signals. The structure provides a foundation for analysis of DM mutations affecting sexual dimorphism and courtship behavior.