Specific Protein-Protein Interaction between Basic Helix-Loop-Helix Transcription Factors and Homeoproteins of the Pitx Family

Abstract

Homeoproteins and basic helix-loop-helix (bHLH) transcription factors are known for their critical role in development and cellular differentiation. The pituitary pro-opiomelanocortin (POMC) gene is a target for factors of both families. Indeed, pituitary-specific transcription of POMC depends on the action of the homeodomain-containing transcription factor Pitx1 and of bHLH heterodimers containing NeuroD1. We now show lineage-restricted expression of NeuroD1 in pituitary corticotroph cells and a direct physical interaction between bHLH heterodimers and Pitx1 that results in transcriptional synergism. The interaction between the bHLH and homeodomains is restricted to ubiquitous (class A) bHLH and to the Pitx subfamily. Since bHLH heterodimers interact with Pitx factors through their ubiquitous moiety, this mechanism may be implicated in other developmental processes involving bHLH factors, such as neurogenesis and myogenesis.

ACKNOWLEDGMENTS

We are grateful to Ming Tsai, François Guillemot, and Harold Weintraub for providing the BETA2, NeuroD1, and MyoD plasmids, respectively. Daniel Durocher was helpful in pull-down experiments. The efficient secretarial assistance of Lise Laroche was much appreciated.

G.P. is a recipient of a Terry Fox Studentship of the National Cancer Institute of Canada. This work was funded by the National Cancer Institute of Canada, supported with funds provided by the Canadian Cancer Society.