Regulation of ZEB1 promoter

LORENZATTI, GUADALUPE; CAVALLO, NATALIA; CABANILLAS, ANA MARIA

Mar del Plata, Buenos Aires, Argentina

Congreso; XLIII Reunión Anual SAIB; 2007

Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB)

REGULATION OF ZEB1 PROMOTER LORENZATTI G, CAVALLO N & CABANILLAS AM Dpto Bioquímica Clínica, CIBICI-CONICET, Facultad Ciencias Químicas, Universidad Nacional de Córdoba ZEB1 is a transcription factor involved in lymphopoiesis T, neurogenesis and myogenesis. Deletion analysis of the ZEB1 promoter localized a proximal G-string critically required for transactivation. Analysis of the G-rich element with TRANSFAC identified consensus binding sites for Runx1, Sp1 and MZF1 and two ZEB1 binding sites. We demonstrated that ZEB1 is able to repress expression of its own gene by binding to one of these sites. In addition, we observed that the activity of ZEB1 protein is regulated by changes of phosphorylation. The aim of this work was to test the transcriptional effect of the putative ZEB1 regulators Runx1, Sp1 and MZF1 on ZEB1 promoter activity. Cell lines expressing ZEB1 (CHO-K1, COS-7) were transfected with Runx1, MZF-1 or Sp1 expression vectors and ZEB1 luciferase promoter (Z1p.212Luc) by Ca-P precipitation. Data are expressed as activation relative to Z1p.12Luc (control).  Z1p.212 was activated 3-fold above Z1p.12Luc by Runx1 and 5-fold by Sp1. MZF1 repressed ZEB1 promoter to 50%. No effect of the factors was observed in absence of the G-string in ZEB1 promoter. Runx1 (absolutely required for the T and B cell lineages) and Sp1 (ubiquitous factor implicated in lymphopoiesis) may act in part by activating the ZEB1 gene through the G-string. MZF1 is a repressor involved in granulopoiesis that may prevent expression of ZEB1 in the myeloid lineage.