Sexual dimorphism in diverse metazoans is regulated by a novel class of intertwined zinc fingers.

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 Dev

journal_title

Genes & development

authors

Zhu L,Wilken J,Phillips NB,Narendra U,Chan G,Stratton SM,Kent SB,Weiss MA

subject

Has Abstract

pub_date

2000-07-15 00:00:00

pages

1750-64

issue

14

eissn

0890-9369

issn

1549-5477

journal_volume

14

pub_type

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