The Drosophila homolog of Onecut homeodomain proteins is a neural-specific transcriptional activator with a potential role in regulating neural differentiation

Mech Dev. 2000 Oct;97(1-2):57-72. doi: 10.1016/s0925-4773(00)00431-7.

Abstract

We report here the characterization of the Drosophila homolog of the onecut homeobox gene, which encodes a protein product with one cut domain and one homeodomain. We present evidence that D-Onecut can bind to similar DNA sequences with high specificity and affinity as other Onecut proteins through the highly conserved cut domain and homeodomain. Interestingly, the cut domain alone can mediate DNA-binding, but the homeodomain cannot. However, depending upon the promoter context, we observed cooperative interactions between the two domains to confer high DNA-binding affinity and specificity. D-Onecut appears to be a moderate transcriptional activator and functions as a nuclear protein in neuronal tissues of both the CNS and PNS during development and in the adult. In the eye, D-Onecut expression is independent of glass, a transcriptional regulator of R cell differentiation. Taken together, our results suggest a role for D-Onecut in the regulation of some aspects of neural differentiation or maintenance. In support of this notion, overexpression of a putative dominant negative form of D-Onecut during eye development does not affect early cell fate specification, but severely affects photoreceptor differentiation.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Binding Sites
  • Cell Differentiation
  • DNA / metabolism
  • DNA, Complementary
  • DNA-Binding Proteins / metabolism
  • Drosophila / genetics
  • Drosophila / metabolism
  • Drosophila / physiology
  • Drosophila Proteins*
  • Enhancer Elements, Genetic
  • Eye / embryology
  • Gene Expression Regulation
  • Genes, Insect
  • Genes, Reporter
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism
  • Homeodomain Proteins / physiology*
  • Humans
  • Insect Proteins / genetics
  • Insect Proteins / metabolism
  • Insect Proteins / physiology*
  • Luciferases / genetics
  • Mice
  • Molecular Sequence Data
  • Nerve Tissue Proteins*
  • Neurons / cytology*
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Nuclear Proteins / physiology*
  • Photoreceptor Cells, Invertebrate / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Homology, Amino Acid
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Trans-Activators / physiology*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Zinc Fingers

Substances

  • DNA, Complementary
  • DNA-Binding Proteins
  • Drosophila Proteins
  • En protein, Drosophila
  • Homeodomain Proteins
  • Insect Proteins
  • Nerve Tissue Proteins
  • Nuclear Proteins
  • Recombinant Fusion Proteins
  • Trans-Activators
  • Transcription Factors
  • gl protein, Drosophila
  • onecut protein, Drosophila
  • DNA
  • Luciferases

Associated data

  • GENBANK/AF169227