The metabolic activator FOXO1 binds hepatitis B virus DNA and activates its transcription.
Hepatitis B virus (HBV) is a small DNA virus that targets the liver and infects humans worldwide. Recently we have shown that the metabolic regulator PGC-1alpha coactivates HBV transcription thereby rendering the virus susceptible to fluctuations in the nutritional status of the liver. PGC-1alpha coactivation of HBV is mediated through the liver-enriched nuclear receptor HNF4alpha and through another yet unknown transcription factor(s). Here we show that the forkhead transcription factor FOXO1, a known target for PGC-1alpha coactivation and a central mediator of glucose metabolism in the liver, binds HBV core promoter and activates its transcription. This activation is further enhanced in the presence of PGC-1alpha, implying that FOXO1 is a target for PGC-1alpha coactivation of HBV transcription. Thus, our results identify another key metabolic regulator as an activator of HBV transcription, thereby supporting the principle that HBV gene expression is regulated in a similar way to key hepatic metabolic genes.
Shlomai
Amir
A
Department of Molecular Genetics, Weizmann Institute of Science, Rehovot, Israel. amirsh@tasmc.health.gov.il
Shaul
Yosef
Y
D002460:Cell Line; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D015967:Gene Expression Regulation, Viral; D006360:Heat-Shock Proteins / Q000378:metabolism; D006515:Hepatitis B virus / Q000235:genetics*; D051557:Hepatocyte Nuclear Factor 4 / Q000378:metabolism; D006801:Humans; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014758:Viral Core Proteins / Q000235:genetics*
D004279:DNA, Viral; C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C496592:HNF4A protein, human; D006360:Heat-Shock Proteins; D051557:Hepatocyte Nuclear Factor 4; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors; D014758:Viral Core Proteins