Binding of nuclear factor EF-C to a functional domain of the hepatitis B virus enhancer region.

Ostapchuk, Philomena; Scheirle, G; Hearing, Patrick

doi:10.1128/mcb.9.7.2787

Cited by 62 publications

(114 citation statements)

References 59 publications

(58 reference statements)

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“…A major protected area corresponds to the previously characterized EP element. The protected G-residues are identical to that reported for the in vitro DMS footprinting of the EP (EF-C) element (Ostapchuk et al, 1989), suggesting that the EP element in both cells bind at least the RFX1 protein (Blake et al, 1996;Katan et al, 1997;Siegrist et al, 1993). In PLC/PRF/5 cells, the analysed EP element has an additional contact point with the binding protein at the non-coding strand due to a T to C transition.…”

Section: Discussionsupporting

confidence: 64%

HBV integrants of hepatocellular carcinoma cell lines contain an active enhancer

2001

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Hepatitis B virus (HBV) infection is a major risk factor worldwide for the development of hepatocellular carcinoma (HCC). Integrated HBV DNA fragments, often highly rearranged, are frequently detected in HCC. In woodchuck, the viral enhancer plays a central role in hepatocarcinogenesis, but in humans the mechanism of HBV oncogenesis has not been established. In this study we investigated the status of the viral enhancer in two human HCC cell lines, Hep3B and PLC/PRF/5 each containing one or more integrated HBV DNA fragments. Active enhancer was de®ned by virtue of its protein occupancy as determined by genomic in vivo DMS footprinting. In PLC/ PRF/5 cells, the HBV DNA was integrated in a cellular gene at chromosome 11q13, at a locus reported to be ampli®ed in many tumors. We show here that in both cell lines, the integrated HBV DNA fragments contain an active enhancer-I. In particular, the occupation of the two previously de®ned basic enhancer elements, E and EP, was prominent. While in both cell lines the same protein binds to the EP elements, the E element, however, is occupied in a cell-line speci®c manner. In PLC/PRF/5 but not Hep3B, the prominent binding of an unde®ned protein was detected. Our data suggest that this protein is likely to be the fetoprotein transcription factor (FTF). The ®nding that enhancer sequences are conserved and functional in di erent cell lines suggests a selection pressure for their long-term maintenance. We therefore propose that the HBV enhancer-I might play a role in hepatocellular carcinogenesis. Oncogene (2001) 20, 6811 ± 6819.

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Section: Discussionsupporting

confidence: 64%

HBV integrants of hepatocellular carcinoma cell lines contain an active enhancer

2001

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“…Obviously, the most immediate aim is to de®ne the role of the kinase domain in the transcription machinery. In contrast to the positive role of EP in viral enhancers, the EP-DNA element, as a multimer and an isolation, does not activate transcription (Ostapchuk et al, 1989;Dikstein et al, 1990;Reinhold et al, 1995;Labrie et al, 1995;Safrany and Perry, 1995;Katan et al, 1997). RFX1 itself contains several independent functional domains.…”

Section: Discussionmentioning

confidence: 90%

“…EP is a key functional element of the hepatitis B virus (HBV) enhancer (Ostapchuk et al, 1989;Zhang et al, 1990aZhang et al, ,b, 1991Dikstein et al, 1990). A second component of the EP nucleo-protein complex is RFX1.…”

Section: Introductionmentioning

confidence: 99%

The kinase activity of c-Abl but not v-Abl is potentiated by direct interaction with RFXI, a protein that binds the enhancers of several viruses and cell-cycle regulated genes

Agami

Shaul

1998

Oncogene

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c-Abl, the non-receptor tyrosine kinase is associated with EP, a DNA element found in promoters/enhancers of di erent viruses and cell-cycle regulated genes. EP-DNA binds RFXI, a member of a novel family of DNA-binding proteins that is conserved through evolution and in yeast, it controls di erentiation and exit from the mitotic cycle to G 0 . EP-associated proteins are preferentially tyrosine phosphorylated and the associated c-Abl has strong tyrosine kinase activity. Here we investigated the molecular mechanism underlying this c-Abl kinase activity. We show that RFXI and c-Abl are in direct interaction, in vitro and in cell extracts, through the RFXI proline rich (PxxP) motif and the c-Abl SH3 domain. Remarkably, this interaction signi®cantly potentiates cAbl but not v-Abl auto-kinase activity. Collectively, we describe a novel mechanism of c-Abl recruitment to a de®ned DNA-cis element with its concomitant kinase activation. We propose that this mechanism may act to regulate cell-cycle control genes.

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“…The binding sites of transcriptional factors on the HBV enhancer have been studied extensively (Ben-Levy et al, 1989;Faktor et al, 1990;Ostapchuk et al, 1989;Patel et al, 1989;Shaul & Ben-Levy, 1987). The HE3 fragment contains recognition sequences for three transcriptional factors: C/EBP, AP-1 and NF-1 ( Fig.…”

Section: The Requirement O F An Intact Nf-l-binding Site For the Inhimentioning

confidence: 99%

“…They initiate transcription of various HBV genes and are regulated by the HBV enhancer (Antonucci & Rutter, 1989;Honigwachs et al, 1989;Yaginuma & Koike, 1989). The HBV enhancer, which is located between the end of the surface antigen gene and the beginning of the X gene, binds both ubiquitous and tissue-specific transcription factors that control the expression of HBV genes (Antonucci & Rutter, 1989;Ben-Levy et al, 1989;Jameel & Siddiqui, 1986;Ostapchuk et al, 1989;Patel et al, 1989;Shaul & Ben-Levy, 1987;Shaul et al, 1985).…”

Section: Introductionmentioning

confidence: 99%

Repression of the hepatitis B virus enhancer by a cellular factor

Spandau

Lee²

1992

Journal of General Virology

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The enhancer element of hepatitis B virus (HBV) regulates the transcription of all HBV mRNA, including the pregenomic mRNA used during replication. This pregenomic mRNA is transcribed from the core gene promoter which is located 500 bp downstream from the HBV enhancer element. To examine the effect of the HBV enhancer on the activity of the core gene promoter, we constructed various plasmids containing different combinations of HBV enhancer and core gene promoter sequences regulating the expression of the chloramphenicol acetyltransferase gene. When the HBV enhancer was positioned immediately adjacent to the core gene promoter, the enhancer increased the activity of the core gene promoter nearly 30-fold. In contrast, the HBV enhancer only modestly stimulated the core gene promoter (less than threefold) at its native position in the HBV genome. This weak HBV enhancer activity was due to a DNA sequence located between the enhancer and the core gene promoter and not due to the increased distance between the enhancer and the core gene promoter. Competition experiments demonstrated that a trans-acting factor(s) bound this sequence and repressed the enhancer. This DNA sequence contains the C/EBP, AP-1 and NF-1 regulatory sites. No inhibition of enhancer activity was observed when only the AP-1 and C/EBP sites were present. Repression of the HBV enhancer was not detected when the NF-1 site was disrupted, indicating that the NF-1 site was involved in the suppression of the HBV enhancer.

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Binding of nuclear factor EF-C to a functional domain of the hepatitis B virus enhancer region.

Cited by 62 publications

References 59 publications

HBV integrants of hepatocellular carcinoma cell lines contain an active enhancer

HBV integrants of hepatocellular carcinoma cell lines contain an active enhancer

The kinase activity of c-Abl but not v-Abl is potentiated by direct interaction with RFXI, a protein that binds the enhancers of several viruses and cell-cycle regulated genes

Repression of the hepatitis B virus enhancer by a cellular factor

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