Transcriptional regulation of the Drosophila caudal homeobox gene by DRE/DREF.
The caudal-related homeobox transcription factors are required for the normal development and differentiation of intestinal cells. Recent reports indicate that misregulation of homeotic gene expression is associated with gastrointestinal cancer in mammals. However, the molecular mechanisms that regulate expression of the caudal-related homeobox genes are poorly understood. In this study, we have identified a DNA replication-related element (DRE) in the 5' flanking region of the Drosophila caudal gene. Gel-mobility shift analysis reveals that three of the four DRE-related sequences in the caudal 5'-flanking region are recognized by the DRE-binding factor (DREF). Deletion and site-directed mutagenesis of these DRE sites results in a considerable reduction in caudal gene promoter activity. Analyses with transgenic flies carrying a caudal-lacZ fusion gene bearing wild-type or mutant DRE sites indicate that the DRE sites are required for caudal expression in vivo. These findings indicate that DRE/DREF is a key regulator of Drosophila caudal homeobox gene expression and suggest that DREs and DREF contribute to intestinal development by regulating caudal gene expression.
Choi
Yoon-Jeong
YJ
Department of Molecular Biology, College of Natural Science and Research Institute of Genetic Engineering, Pusan National University, Busan 609-735, Korea.
Choi
Tae-Young
TY
Yamaguchi
Masamitsu
M
Matsukage
Akio
A
Kim
Young-Shin
YS
Yoo
Mi-Ae
MA
D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins; D005786:Gene Expression Regulation; D017344:Genes, Insect; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D020218:Response Elements; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
C099494:Dref protein, Drosophila; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D014157:Transcription Factors; C084564:cad protein, Drosophila