Transcriptional activation and repression by cellular DNA-binding protein C/EBP

Pei, Duanqing; Shih, Chiaho

doi:10.1128/jvi.64.4.1517-1522.1990

Cited by 67 publications

(27 citation statements)

References 40 publications

(47 reference statements)

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“…7), competition among protein factors for binding to this site may be an important way for HBV to regulate EnhI enhancer and X promoter activities. In this regard, it is interesting to note that C/EBP down-regulates (16) and AP1 up-regulates (3) EnhI enhancer activity. Since EnhI can increase the downstream C promoter activity by about 60-fold (unpublished observation) and has only a marginal 2to 3-fold activity on the X promoter ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…This site has no enhancer activity by itself but displays a weak ubiquitous enhancer activity when oligomerized (4). The E site can be bound by several protein factors, including C/EBP (11,16), AP1 (4), and CREB (4), and is thought to be an essential component of the EnhI enhancer (2, 4). A third protein factor binding site, named the EP site, is located upstream of the E site (1).…”

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confidence: 99%

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Characterization of the hepatitis B virus EnhI enhancer and X promoter complex

Guo

Bell

1991

J Virol

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The hepatitis B virus EnhI enhancer element overlaps the promoter of the X gene. By performing methylation interference experiments, four protein factor binding sites clustered in a 120-bp region were found to control the EnhI enhancer and X promoter activities. Deletion mapping experiments indicated that the two upstream protein factor binding sites constituted a basal enhancer module. This module, likely bound by a liver-specific factor and a ubiquitous factor, could activate the herpes simplex virus thymidine kinase gene promoter by 5- or 10-fold, depending on the orientation, in Huh7 cells, a liver-derived cell line, but not in other cell types tested. The two downstream protein factor binding sites interact with the upstream basal enhancer module in an orientation- and distance-dependent manner to increase the enhancer activity by another 10-fold. In addition, at least one of the two downstream protein factor binding sites is also essential for the X promoter activity.

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Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Characterization of the hepatitis B virus EnhI enhancer and X promoter complex

Guo

Bell

1991

J Virol

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“…The identification of host factors that interact with the HBV DNA genome has made significant contributions to our understanding of mechanisms that regulate HBV gene expression. Indeed, both liver‐enriched and ubiquitous transcription factors, such as hepatocyte nuclear factor 1 (HNF1), HNF3, HNF4, CCAAT enhancer‐binding protein (C/EBP), chicken ovalbumin upstream promoter transcription factor (COUP‐TF), nuclear transcription factor Y (NF‐Y), and specificity protein 1 (Sp1), have been shown to regulate the expression of the S and C genes 5‐13. The liver specificity of the preS1 promoter, the major surface promoter, and the core promoter is attributed to the need of liver‐enriched transcription factors for their activities 10, 14‐18…”

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confidence: 99%

Krüppel-like factor 15 activates hepatitis B virus gene expression and replication

et al. 2011

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Hepatitis B virus (HBV) is a small DNA virus that requires cellular transcription factors for the expression of its genes. To understand the molecular mechanisms that regulate HBV gene expression, we conducted a yeast one-hybrid screen to identify novel cellular transcription factors that may control HBV gene expression. Here we demonstrate that Krüpple-like factor 15 (KLF15), a liver-enriched transcription factor, can robustly activate HBV surface and core promoters. Mutations in the putative KLF15 binding site in the HBV core promoter abolished the ability of KLF15 to activate core promoter in luciferase assays. Furthermore, the overexpression of KLF15 stimulated the expression of HBV surface antigen (HBsAg) and the core protein and enhanced viral replication. Conversely, siRNA knockdown of the endogenous KLF15 in Huh7 cells resulted in a reduction in HBV surface and core promoter activities. In electrophoretic mobility shift and chromatin immunoprecipitation assays KLF15 binds to DNA probes derived from the core promoter and the surface promoter. Introduction of an expression vector for KLF15 shRNA together with the HBV genome into the mouse liver using hydrodynamic injection resulted in a significant reduction in viral gene expression and DNA replication. Additionally, mutations in the KLF15 response element in the HBV core promoter significantly reduced viral DNA levels in the mouse serum. Conclusion KLF15 is a novel transcriptional activator for HBV core and surface promoters. It is possible that KLF15 may serve as a potential therapeutic target to reduce HBV gene expression and viral replication.

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“…Each RNA is transcribed from its own promoter and terminates at a common polyadenylation site (16,52,72). The structure and function of the four HBV promoters have been quite extensively characterized, and it is apparent that liver-specific expression from the enhancer 1/X gene, nucleocapsid, and large surface antigen promoters results from the combinatorial action of multiple liver-enriched transcription factors, including C/EBP, HNF1, HNF3, and HNF4, binding to the regulatory sequence elements of these promoters (5,9,12,17,20,27,35,36,44,47,50,57,75,80). The reason why transcription of the major surface antigen RNA is restricted to hepatocytes in vivo is currently unclear, as the identified regulatory sequence elements of the major surface antigen promoter bind ubiquitous transcription factors (51,61).…”

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confidence: 99%

Members of the nuclear receptor superfamily regulate transcription from the hepatitis B virus nucleocapsid promoter

Raney

Johnson

Palmer

et al. 1997

J Virol

155

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The role of members of the nuclear receptor superfamily of transcription factors in regulating hepatitis B virus (HBV) transcription was investigated. Hepatocyte nuclear factor 4 (HNF4), the retinoid X receptor (RXR), and the peroxisome proliferator-activated receptor (PPAR) were examined for their capacity to modulate the level of transcriptional activity from the four HBV promoters by transient-transfection analysis in the dedifferentiated hepatoma cell line, HepG2.1. It was found that the nucleocapsid and large surface antigen promoters were transactivated in the presence of HNF4 whereas the enhancer I/X gene, nucleocapsid, and large surface antigen promoters were transactivated in the presence of RXR and PPAR. Characterization of the nuclear receptors interacting with the nucleocapsid promoter region demonstrated that HNF4 is the primary transcription factor binding to the regulatory region spanning nucleotides ؊127 to ؊102 whereas HNF4, RXR-PPAR heterodimers, COUPTF1, and ARP1 bind the regulatory region spanning nucleotides ؊34 to ؊7. Transcriptional transactivation from the nucleocapsid promoter by HNF4 appears to be mediated through the two HNF4 binding sites in the promoter, whereas modulation of the level of transcription from the nucleocapsid promoter by RXR-PPAR appears to be regulated by the regulatory sequence element spanning nucleotides ؊34 to ؊7 and the HBV enhancer 1 region. These observations indicate that HBV transcription, and pregenomic RNA synthesis in particular, is regulated by ligand-dependent nuclear receptors. Agonists and antagonists capable of regulating the activity of these nuclear receptors may permit the modulation of HBV transcription and consequently replication during viral infection.

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Transcriptional activation and repression by cellular DNA-binding protein C/EBP

Cited by 67 publications

References 40 publications

Characterization of the hepatitis B virus EnhI enhancer and X promoter complex

Characterization of the hepatitis B virus EnhI enhancer and X promoter complex

Krüppel-like factor 15 activates hepatitis B virus gene expression and replication

Members of the nuclear receptor superfamily regulate transcription from the hepatitis B virus nucleocapsid promoter

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