Hox gene products modulate the DNA binding activity of Pbx1 and Pbx2

M A van Dijk1, L T Peltenburg, C Murre

  • 1Department of Biology, University of California, San Diego, La Jolla 92093, USA.

Insights

Vertebrate Hox and Pbx proteins, including Pbx1 and Pbx2, bind cooperatively to DNA. This interaction is modulated by Engrailed-2 and is retained in the E2A-Pbx1 leukemia-associated protein.

Area of Science:

  • Molecular Biology
  • Genetics
  • Developmental Biology

Background:

  • A novel family of homeodomain proteins, including extradenticle, ceh-20, and mammalian Pbx1-3, has been identified.
  • Homeodomain proteins play critical roles in gene regulation and development.

Purpose of the Study:

  • To investigate the DNA-binding interactions between members of the Pbx protein family and Hox proteins.
  • To determine the role of Engrailed-2 in modulating Pbx protein DNA binding.
  • To examine the interaction of the chimeric E2A-Pbx1 protein with Hox proteins.

Main Methods:

  • Co-immunoprecipitation assays to assess protein-protein interactions.
  • Electrophoretic mobility shift assays (EMSAs) to study DNA binding.
  • Analysis of DNA binding activity of wild-type and chimeric proteins.

Main Results:

  • Pbx1 and Pbx2 proteins bind cooperatively to DNA in conjunction with Hoxb-7 and Hoxb-8.
  • Engrailed-2 influences the DNA binding of Pbx proteins at specific target sites.
  • The leukemia-associated chimera E2A-Pbx1 maintains its capacity to interact with Hox proteins.

Conclusions:

  • Vertebrate Hox and Pbx gene products exhibit cooperative DNA binding capabilities.
  • These interactions are crucial for gene regulation in development and disease.
  • Pbx proteins are key partners for Hox proteins in transcriptional regulation.

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