Abstract:
: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.
journal_name
Genes Devjournal_title
Genes & developmentauthors
Zhu L,Wilken J,Phillips NB,Narendra U,Chan G,Stratton SM,Kent SB,Weiss MAsubject
Has Abstractpub_date
2000-07-15 00:00:00pages
1750-64issue
14eissn
0890-9369issn
1549-5477journal_volume
14pub_type
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