For COVID-19 vaccine updates, please review our information guide. For patient eligibility and scheduling availability, please visit VaccineTogetherNY.org.

Three isoforms of a hepatocyte nuclear factor-4 transcription factor with tissue- and stage-specific expression in the adult mosquito.

TitleThree isoforms of a hepatocyte nuclear factor-4 transcription factor with tissue- and stage-specific expression in the adult mosquito.
Publication TypeJournal Article
Year of Publication1998
AuthorsKapitskaya MZ, Dittmer NT, Deitsch KW, Cho WL, Taylor DG, Leff T, Raikhel AS
JournalJ Biol Chem
Volume273
Issue45
Pagination29801-10
Date Published1998 Nov 06
ISSN0021-9258
KeywordsAedes, 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.

DOI10.1074/jbc.273.45.29801
Alternate JournalJ Biol Chem
PubMed ID9792695
Grant ListAI-24716 / AI / NIAID NIH HHS / United States

Weill Cornell Medicine Microbiology and Immunology 1300 York Avenue, Box 62 New York, NY 10065 Phone: (212) 746-6505 Fax: (212) 746-8587