Sex-specific gene regulation: The doublesex DM motif is a bipartite DNA-binding domain

Uma Narendra, Lingyang Zhu, Biaoru Li, Jill Wilken, Michael A. Weiss

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Sex-specific gene expression in Drosophila melanogaster is regulated in part by the Doublesex (DSX) transcription factor. Male- and female-specific splicing isoforms share a novel DNA-binding domain, designated the DM motif. This domain is conserved among a newly recognized family of vertebrate transcription factors involved in developmental patterning and sex determination. The DM motif consists of an N-terminal zinc module and a disordered C-terminal tail, hypothesized to fold on specific DNA binding as a recognition α-helix. Truncation of the tail does not perturb the structure of the zinc module but impairs DNA binding and DNA-dependent dimerization. Chemical protein synthesis and alanine scanning mutagenesis are employed to test the contributions of 13 side chains to specific DNA binding. Selected arginine or lysine residues in the zinc module were substituted by norleucine, an isostere that maintains the aliphatic portion of the side chain but lacks a positive charge. Arginine or glutamine residues in the tail were substituted by alanine. Evidence is obtained that both the zinc module and C-terminal tail contribute to a bipartite DNA-binding surface. Conserved arginine and glutamine residues in the tail are required for high affinity DNA recognition, consistent with its proposed role as a nascent recognition α-helix.

Original languageEnglish (US)
Pages (from-to)43463-43473
Number of pages11
JournalJournal of Biological Chemistry
Volume277
Issue number45
DOIs
StatePublished - Nov 8 2002
Externally publishedYes

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Gene expression
Tail
DNA
Zinc
Genes
Arginine
Glutamine
Alanine
Transcription Factors
Norleucine
Mutagenesis
Dimerization
Drosophila melanogaster
Lysine
Vertebrates
Protein Isoforms
Scanning
Gene Expression
Proteins

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Sex-specific gene regulation : The doublesex DM motif is a bipartite DNA-binding domain. / Narendra, Uma; Zhu, Lingyang; Li, Biaoru; Wilken, Jill; Weiss, Michael A.

In: Journal of Biological Chemistry, Vol. 277, No. 45, 08.11.2002, p. 43463-43473.

Research output: Contribution to journalArticle

Narendra, Uma ; Zhu, Lingyang ; Li, Biaoru ; Wilken, Jill ; Weiss, Michael A. / Sex-specific gene regulation : The doublesex DM motif is a bipartite DNA-binding domain. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 45. pp. 43463-43473.
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