Title | Three isoforms of a hepatocyte nuclear factor-4 transcription factor with tissue- and stage-specific expression in the adult mosquito. |
Publication Type | Journal Article |
Year of Publication | 1998 |
Authors | Kapitskaya MZ, Dittmer NT, Deitsch KW, Cho WL, Taylor DG, Leff T, Raikhel AS |
Journal | J Biol Chem |
Volume | 273 |
Issue | 45 |
Pagination | 29801-10 |
Date Published | 1998 Nov 06 |
ISSN | 0021-9258 |
Keywords | Aedes, Amino Acid Sequence, Animals, Base Sequence, Cell Line, Cloning, Molecular, DNA Probes, Female, Hepatocyte Growth Factor, Humans, Isomerism, Molecular Sequence Data, Repressor Proteins, RNA, Messenger, Sequence Homology, Amino Acid |
Abstract | We cloned three isoforms of hepatocyte nuclear factor-4 (HNF-4) from the mosquito Aedes aegypti, designated AaHNF-4a, AaHNF-4b, and AaHNF-4c. AaHNF-4a and AaHNF-4b are typical members of the HNF-4 subfamily of nuclear receptors with high amino acid conservation. They differ in N-terminal regions and exhibit distinct developmental profiles in the female mosquito fat body, a metabolic tissue functionally analogous to the vertebrate liver. The AaHNF-4b mRNA is predominant during the previtellogenic and vitellogenic phases, while the AaHNF-4a mRNA is predominant during the termination phase of vitellogenesis, coinciding with the onset of lipogenesis. The third isoform, AaHNF-4c, lacks part of the A/B and the entire C (DNA-binding) domains. The AaHNF-4c transcript found in the fat body during the termination of vitellogenesis may serve as a transcriptional inhibitor. Both AaHNF-4a and AaHNF-4b bind to the cognate DNA recognition site in electrophoretic mobility shift assay. Dimerization of AaHNF-4c with other mosquito HNF-4 isoforms or with mammalian HNF-4 prevents binding to the HNF-4 response element. In transfected human 293T cells, AaHNF-4c significantly reduced the transactivating effect of the human HNF-4alpha1 on the apolipoprotein CIII promoter. Electrophoretic mobility shift assay confirmed the presence of HNF-4 binding sites upstream of A. aegypti vg and vcp, two yolk protein genes expressed in the female mosquito fat body during vitellogenesis. Therefore, HNF-4, an important regulator of liver-specific genes, plays a critical role in the insect fat body. |
DOI | 10.1074/jbc.273.45.29801 |
Alternate Journal | J Biol Chem |
PubMed ID | 9792695 |
Grant List | AI-24716 / AI / NIAID NIH HHS / United States |
Submitted by mam2155 on March 24, 2014 - 4:11pm