PBX and MEIS as non-DNA-binding partners in trimeric complexes with HOX proteins

Area of Science:

• Molecular Biology
• Genetics
• Biochemistry

Background:

• HOX, PBX, and MEIS are transcription factors that bind DNA via a homeodomain.
• PBX proteins form heterodimers with MEIS and certain HOX proteins.
• MEIS proteins form heterodimers with specific HOX proteins.

Purpose of the Study:

• To investigate the dimeric and higher-order interactions among HOX, PBX, and MEIS transcription factors.
• To elucidate the structural and functional aspects of these protein complexes.
• To identify novel roles of PBX and MEIS in modulating DNA-binding interactions.

Main Methods:

• Analysis of protein-protein interactions.
• Investigation of DNA binding affinities.
• Examination of protein complex formation in vitro and in vivo.
• Mutational analysis of protein domains.

Main Results:

• PBX N-terminal regions are crucial for cooperative binding with HOXD4 and HOXD9.
• MEIS and PBX form higher-order complexes on heterodimeric binding sites.
• MEIS can form trimers with DNA-bound PBX-HOX heterodimers, acting as a non-DNA-binding partner.
• HOXD4 N-terminus negatively regulates trimer formation.
• Trimer stability is enhanced compared to heterodimers.
• PBX interacts with both MEIS and HOX proteins in specific trimer formations.

Conclusions:

• PBX and MEIS play significant roles in forming higher-order transcription factor complexes.
• These interactions lead to novel regulatory functions in modulating DNA-bound heterodimers.
• Findings suggest new mechanisms for transcriptional regulation involving these homeodomain proteins.