Regulation of aquaporin-2 gene transcription by GATA-3. off.
To evaluate the functional role of GATA motifs in the 5'-flanking region of a kidney-specific AQP-2 water channel gene, we sought to isolate a GATA factor(s) expressed in collecting ducts and determined the role on the AQP-2 promoter. Two cDNAs encoding GATA factors were isolated from rat kidney, whose sequences were highly homologous with human GATA-2 and -3. Reverse-transcription PCR using dissected nephron segments revealed that rat GATA-3 but not GATA-2 was expressed in collecting ducts, thus indicating that GATA-3 could interact with GATA motifs in the AQP-2 promoter. Transactivation experiments utilizing the rat GATA-3 expression vector indicated that rat GATA-3 increased the AQP-2 promoter activity about fourfold. These results indicated that GATA motifs in the 5'-flanking region of the hAQP-2 gene were functional cis-elements and that GATA-3 in collecting ducts may be one of the important regulators of AQP-2 expression in vivo.
Uchida
S
S
Second Department of Internal Medicine, School of Medicine, Tokyo Medical and Dental University, Japan. suchida.med2@med.tmd.ac.jp
Matsumura
Y
Y
Rai
T
T
Sasaki
S
S
Marumo
F
F
D000818:Animals; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D050989:GATA2 Transcription Factor; D050990:GATA3 Transcription Factor; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D009399:Nephrons / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D051381:Rats; D015534:Trans-Activators / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic / Q000502:physiology*
C496023:AQP2 protein, human; C496025:Aqp2 protein, rat; D051399:Aquaporin 2; D051403:Aquaporin 6; D020346:Aquaporins; D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D050989:GATA2 Transcription Factor; C494711:GATA2 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; C494713:Gata2 protein, rat; D007473:Ion Channels; D015534:Trans-Activators; D014157:Transcription Factors