The Caudal homeodomain protein activates Drosophila E2F gene expression

Abstract

The Drosophila caudal homeobox gene is required for definition of the anteroposterior axis and for gut development, and CDX1 and CDX2, human homologs, play crucial roles in the regulation of cell proliferation and differentiation in the intestine. Most studies have indicated tumor suppressor functions of Cdx2, with inhibition of proliferation, while the effects of Cdx1 are more controversial. The influence of Drosophila Caudal on cell proliferation is unknown. In this study, we found three potential Caudal binding sequences in the 5'-flanking region of the Drosophila E2F (DE2F) gene and showed by transient transfection assays that they are involved in Caudal transactivation of the dE2F gene promoter. Analyses with transgenic flies carrying an E2F-lacZ fusion gene, with and without mutation in the Caudal binding site, indicated that the Caudal binding sites are required for expression of dE2F in living flies. Caudal-induced E2F expression was also confirmed with a GAL4-UAS system in living flies. In addition, ectopic expression of Caudal with heat-shock promotion induced melanotic tumors in larvae. These results suggest that Caudal is involved in regulation of proliferation through transactivation of the E2F gene in Drosophila.

The Drosophila wing differentiation factor Vestigial–Scalloped is required for cell proliferation and cell survival at the dorso-ventral boundary of the wing imaginal disc

“…45 In addition, the Caudal (CAD) homeodomain protein was shown to bind the dE2F promoter in vitro, and CAD binding sites in the dE2F promoter are required for expression of dE2F in living flies. 46 These results most clearly demonstrate that developmental genes like Cad, Hh and Hox can directly regulate cell growth and proliferation. There are several indications that the vg gene can induce cell proliferation when expressed ectopically, 4,47 and may mediate the cross-talk between developmental and cell cycle genes in wing development.…”

Regulation of Intestinal Stem Cell Proliferation by Human Methyl-CpG-binding Protein-2 in Drosophila

“…Anesthetized adult flies were sputter-coated with platinum (Kato et al, 2008) hs Heat-shock inducible (Hwang et al, 2002) GMR Eye (Robertson et al, 1988) …”

Identifying Target Genes Regulated Downstream of Cdx2 by Microarray Analysis

“…In Drosophila, E2F gene induction by caudal homeodomain protein is also reported. 20 The E2F family of transcription factor plays a central role in the regulation of gene expression during the G 1 /S phase transition and DNA replication, as well as the expression of genes involved in apoptosis, DNA repair, and mitosis. 21 -23 The E2F3 may be one of the key factors involved in a role of Cdx2 in regulating cell fate determination in epithelial cells.…”