biostudies-literatureShen ZShanghai Science and Technology CommitteeShanghai Municipal Education CommissionChinese Academy of Medical SciencesNSFCShanghai Shen Kang Hospital Development CenterNational Science and Technology Major Project of China2157-2171https://www.ebi.ac.uk/biostudies/studies/S-EPMC8887475biostudies-literatureUnknown50(4)Chronic infection with hepatitis B virus (HBV) is associated with liver cirrhosis and hepatocellular carcinoma. Upon infection of hepatocytes, HBV covalently closed circular DNA (cccDNA) exists as histone-bound mini-chromosome, subjected to transcriptional regulation similar to chromosomal DNA. Here we identify high mobility group AT-hook 1 (HMGA1) protein as a positive regulator of HBV transcription that binds to a conserved ATTGG site within enhancer II/core promoter (EII/Cp) and recruits transcription factors FOXO3α and PGC1α. HMGA1-mediated upregulation of EII/Cp results in enhanced viral gene expression and genome replication. Notably, expression of endogenous HMGA1 was also demonstrated to be upregulated by HBV, which involves HBV X protein (HBx) interacting with SP1 transcription faNucleic acids researchHigh mobility group AT-hook 1 (HMGA1) is an important positive regulator of hepatitis B virus (HBV) that is reciprocally upregulated by HBV X protein.PMC88874752017ZX102022022018ZX103012082018PT31044201701070007E00057821722558197193120QA140180081971921SHDC12019116321701503157010371Wu JLiu JShen ZXie YChen JHe JGuo YZhang JDeng QGao ZZhang SfalseHigh mobility group AT-hook 1 (HMGA1) is an important positive regulator of hepatitis B virus (HBV) that is reciprocally upregulated by HBV X protein.Chronic infection with hepatitis B virus (HBV) is associated with liver cirrhosis and hepatocellular carcinoma. Upon infection of hepatocytes, HBV covalently closed circular DNA (cccDNA) exists as histone-bound mini-chromosome, subjected to transcriptional regulation similar to chromosomal DNA. Here we identify high mobility group AT-hook 1 (HMGA1) protein as a positive regulator of HBV transcription that binds to a conserved ATTGG site within enhancer II/core promoter (EII/Cp) and recruits transcription factors FOXO3α and PGC1α. HMGA1-mediated upregulation of EII/Cp results in enhanced viral gene expression and genome replication. Notably, expression of endogenous HMGA1 was also demonstrated to be upregulated by HBV, which involves HBV X protein (HBx) interacting with SP1 transcription fa2022-01-01T00:00:00Z2022 Feb2026-05-31T02:06:49.535Z2025-04-04T23:03:09.532ZS-EPMC88874753513719110.1093/nar/gkac070