Figure 7. Model for LMO3 and HEN2 cooperation in transcriptional regulation of Mash1 in Neuroblastoma.
HES1 binds to HES1 binding sites and E-box on Mash1 promoter and represses Mash1 transcription. LMO3 inhibits recruitment of HES1 onto HES1-binding sites and E-box on Mash1 promoter by forming complex with HES1. HEN2 interferes with recruitment of HES1 onto HES1-binding sites and E-box on Mash1 promoter by forming complex with HES1 and competing with HES1 in binding to these sites. LMO3 promotes recruitment of HEN2 onto HES1-binding sites and E-box on Mash1 promoter by forming complex with HEN2 but inhibits negative effects of HEN2 on Mash1 promoter. Thereby expression of Mash1 is up-regulated.