RFX1 is Identical to Enhancer Factor C and Functions As a Transactivator of the Hepatitis B Virus Enhancer

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1993 Oct 1

PMID 8413236

Citations 38

Authors

C A Siegrist

B Durand

P Emery

E David

P Hearing

B MACH

W Reith

Affiliations

Soon will be listed here.

Abstract

Hepatitis B virus gene expression is to a large extent under the control of enhancer I (EnhI). The activity of EnhI is strictly dependent on the enhancer factor C (EF-C) site, an inverted repeat that is bound by a ubiquitous nuclear protein known as EF-C. Here we report the unexpected finding that EF-C is in fact identical to RFX1, a novel transcription factor previously cloned by virtue of its affinity for the HLA class II X-box promoter element. This finding has allowed us to provide direct evidence that RFX1 (EF-C) is crucial for EnhI function in HepG2 hepatoma cells; RFX1-specific antisense oligonucleotides appear to inhibit EnhI-driven expression of the hepatitis B virus major surface antigen gene, and in transfection assays, RFX1 behaves as a potent transactivator of EnhI. Interestingly, transactivation of EnhI by RFX1 (EF-C) is not observed in cell lines that are not of liver origin, suggesting that the ubiquitous RFX1 protein cooperates with liver-specific factors.

Citing Articles

Regulatory factor X1 induces macrophage M1 polarization by promoting DNA demethylation in autoimmune inflammation.

Yang S, Du P, Cui H, Zheng M, He W, Gao X JCI Insight. 2023; 8(20.

PMID: 37733446 PMC: 10619507. DOI: 10.1172/jci.insight.165546.

Young SINEs in pig genomes impact gene regulation, genetic diversity, and complex traits.

Zhao P, Gu L, Gao Y, Pan Z, Liu L, Li X Commun Biol. 2023; 6(1):894.

PMID: 37652983 PMC: 10471783. DOI: 10.1038/s42003-023-05234-x.

Host Transcription Factors in Hepatitis B Virus RNA Synthesis.

Turton K, Meier-Stephenson V, Badmalia M, Coffin C, Patel T Viruses. 2020; 12(2).

PMID: 32019103 PMC: 7077322. DOI: 10.3390/v12020160.

RFX1 participates in doxorubicin-induced hepatitis B virus reactivation.

Wang J, Jia J, Chen R, Ding S, Xu Q, Zhang T Cancer Med. 2018; 7(5):2021-2033.

PMID: 29601674 PMC: 5943424. DOI: 10.1002/cam4.1468.

RFX1 and RFX3 Transcription Factors Interact with the D Sequence of Adeno-Associated Virus Inverted Terminal Repeat and Regulate AAV Transduction.

Julien L, Chassagne J, Peccate C, Lorain S, Pietri-Rouxel F, Danos O Sci Rep. 2018; 8(1):210.

PMID: 29317724 PMC: 5760533. DOI: 10.1038/s41598-017-18604-3.

References

Knowles B, HOWE C, Aden D . Human hepatocellular carcinoma cell lines secrete the major plasma proteins and hepatitis B surface antigen. Science. 1980; 209(4455):497-9. DOI: 10.1126/science.6248960. View

Gorman C, Moffat L, Howard B . Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Mol Cell Biol. 1982; 2(9):1044-51. PMC: 369897. DOI: 10.1128/mcb.2.9.1044-1051.1982. View

Dignam J, Lebovitz R, Roeder R . Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei. Nucleic Acids Res. 1983; 11(5):1475-89. PMC: 325809. DOI: 10.1093/nar/11.5.1475. View

Huang L, Wang R, Gama-Sosa M, Shenoy S, Ehrlich M . A protein from human placental nuclei binds preferentially to 5-methylcytosine-rich DNA. Nature. 1984; 308(5956):293-5. DOI: 10.1038/308293a0. View

Tabor S, Richardson C . A bacteriophage T7 RNA polymerase/promoter system for controlled exclusive expression of specific genes. Proc Natl Acad Sci U S A. 1985; 82(4):1074-8. PMC: 397196. DOI: 10.1073/pnas.82.4.1074. View

Shaul Y, Rutter W, Laub O . A human hepatitis B viral enhancer element. EMBO J. 1985; 4(2):427-30. PMC: 554203. DOI: 10.1002/j.1460-2075.1985.tb03646.x. View

Tognoni A, Cattaneo R, Serfling E, Schaffner W . A novel expression selection approach allows precise mapping of the hepatitis B virus enhancer. Nucleic Acids Res. 1985; 13(20):7457-72. PMC: 322055. DOI: 10.1093/nar/13.20.7457. View

Ostapchuk P, Diffley J, Bruder J, Stillman B, Levine A, Hearing P . Interaction of a nuclear factor with the polyomavirus enhancer region. Proc Natl Acad Sci U S A. 1986; 83(22):8550-4. PMC: 386968. DOI: 10.1073/pnas.83.22.8550. View

Wang R, Zhang X, Khan R, Zhou Y, Huang L, Ehrlich M . Methylated DNA-binding protein from human placenta recognizes specific methylated sites on several prokaryotic DNAs. Nucleic Acids Res. 1986; 14(24):9843-60. PMC: 341339. DOI: 10.1093/nar/14.24.9843. View

10.

Elfassi E . Broad specificity of the hepatitis B enhancer function. Virology. 1987; 160(1):259-62. DOI: 10.1016/0042-6822(87)90069-9. View

11.

Twu J, Schloemer R . Transcriptional trans-activating function of hepatitis B virus. J Virol. 1987; 61(11):3448-53. PMC: 255941. DOI: 10.1128/JVI.61.11.3448-3453.1987. View

12.

Spandau D, Lee C . trans-activation of viral enhancers by the hepatitis B virus X protein. J Virol. 1988; 62(2):427-34. PMC: 250552. DOI: 10.1128/JVI.62.2.427-434.1988. View

13.

Ghazal P, Lubon H, Hennighausen L . Multiple sequence-specific transcription factors modulate cytomegalovirus enhancer activity in vitro. Mol Cell Biol. 1988; 8(4):1809-11. PMC: 363343. DOI: 10.1128/mcb.8.4.1809-1811.1988. View

14.

Reith W, Satola S, Sanchez C, Amaldi I, Griscelli C, Hadam M . Congenital immunodeficiency with a regulatory defect in MHC class II gene expression lacks a specific HLA-DR promoter binding protein, RF-X. Cell. 1988; 53(6):897-906. DOI: 10.1016/s0092-8674(88)90389-3. View

15.

Henthorn P, Zervos P, Raducha M, Harris H, Kadesch T . Expression of a human placental alkaline phosphatase gene in transfected cells: use as a reporter for studies of gene expression. Proc Natl Acad Sci U S A. 1988; 85(17):6342-6. PMC: 281966. DOI: 10.1073/pnas.85.17.6342. View

16.

Khan R, Zhang X, Supakar P, Ehrlich K, Ehrlich M . Human methylated DNA-binding protein. Determinants of a pBR322 recognition site. J Biol Chem. 1988; 263(28):14374-83. View

17.

Faktor O, Berger I, Shaul Y . Cellular factors that interact with the hepatitis B virus enhancer. Mol Cell Biol. 1989; 9(4):1804-9. PMC: 362602. DOI: 10.1128/mcb.9.4.1804-1809.1989. View

18.

Reith W, Barras E, Satola S, Kobr M, Reinhart D, Sanchez C . Cloning of the major histocompatibility complex class II promoter binding protein affected in a hereditary defect in class II gene regulation. Proc Natl Acad Sci U S A. 1989; 86(11):4200-4. PMC: 287418. DOI: 10.1073/pnas.86.11.4200. View

19.

Colgrove R, Simon G, Ganem D . Transcriptional activation of homologous and heterologous genes by the hepatitis B virus X gene product in cells permissive for viral replication. J Virol. 1989; 63(9):4019-26. PMC: 250999. DOI: 10.1128/JVI.63.9.4019-4026.1989. View

20.

Ostapchuk P, Scheirle G, Hearing P . Binding of nuclear factor EF-C to a functional domain of the hepatitis B virus enhancer region. Mol Cell Biol. 1989; 9(7):2787-97. PMC: 362744. DOI: 10.1128/mcb.9.7.2787-2797.1989. View