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Synergistic trans-activation of the human C-reactive protein promoter by transcription factor HNF-1 binding at two distinct sites.
EMBO J. 1990 Dec; 9(13):4467-75.EJ

Abstract

The promoter region of the human C-reactive protein (CRP) gene comprises two distinct regions (APREs, for Acute Phase Responsive Elements) each one containing information necessary and sufficient for liver specific and IL-6 inducible expression in human hepatoma Hep3B cells. In this paper we show that both APREs contain a low affinity binding site for the liver specific transcription factor HNF-1/LF-B1. The two sites are separated by approximately 80 bp. Mutations in either of the two sites abolish inducible expression. The same effect is specifically obtained in cotransfection competition experiments when the human albumin HNF-1 site is used as competitor. However, HNF-1 is not the intranuclear mediator of IL-6 because synthetic promoters formed by multimerized copies of different HNF-1 binding sites are not transcriptionally activated by this cytokine. An expression vector encoding full length HNF-1 is capable of trans-activating transcription from the wild-type CRP promoter but not from mutants which have lost the ability to bind HNF-1. Moreover, the level of trans-activation observed with the natural promoter containing both HNF-1 binding sites is far greater than the level of mutated variants containing only one of the two sites. This result strongly suggests that two HNF-1 molecules bound simultaneously to sites distant from each other can act synergistically to activate gene expression.

Authors+Show Affiliations

Dipartmento di Biochimica e Biotecnologie Mediche, II Facoltà di Medicina e Chirurgia, Napoli, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

2265613

Citation

Toniatti, C, et al. "Synergistic Trans-activation of the Human C-reactive Protein Promoter By Transcription Factor HNF-1 Binding at Two Distinct Sites." The EMBO Journal, vol. 9, no. 13, 1990, pp. 4467-75.
Toniatti C, Demartis A, Monaci P, et al. Synergistic trans-activation of the human C-reactive protein promoter by transcription factor HNF-1 binding at two distinct sites. EMBO J. 1990;9(13):4467-75.
Toniatti, C., Demartis, A., Monaci, P., Nicosia, A., & Ciliberto, G. (1990). Synergistic trans-activation of the human C-reactive protein promoter by transcription factor HNF-1 binding at two distinct sites. The EMBO Journal, 9(13), 4467-75.
Toniatti C, et al. Synergistic Trans-activation of the Human C-reactive Protein Promoter By Transcription Factor HNF-1 Binding at Two Distinct Sites. EMBO J. 1990;9(13):4467-75. PubMed PMID: 2265613.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synergistic trans-activation of the human C-reactive protein promoter by transcription factor HNF-1 binding at two distinct sites. AU - Toniatti,C, AU - Demartis,A, AU - Monaci,P, AU - Nicosia,A, AU - Ciliberto,G, PY - 1990/12/1/pubmed PY - 1990/12/1/medline PY - 1990/12/1/entrez SP - 4467 EP - 75 JF - The EMBO journal JO - EMBO J VL - 9 IS - 13 N2 - The promoter region of the human C-reactive protein (CRP) gene comprises two distinct regions (APREs, for Acute Phase Responsive Elements) each one containing information necessary and sufficient for liver specific and IL-6 inducible expression in human hepatoma Hep3B cells. In this paper we show that both APREs contain a low affinity binding site for the liver specific transcription factor HNF-1/LF-B1. The two sites are separated by approximately 80 bp. Mutations in either of the two sites abolish inducible expression. The same effect is specifically obtained in cotransfection competition experiments when the human albumin HNF-1 site is used as competitor. However, HNF-1 is not the intranuclear mediator of IL-6 because synthetic promoters formed by multimerized copies of different HNF-1 binding sites are not transcriptionally activated by this cytokine. An expression vector encoding full length HNF-1 is capable of trans-activating transcription from the wild-type CRP promoter but not from mutants which have lost the ability to bind HNF-1. Moreover, the level of trans-activation observed with the natural promoter containing both HNF-1 binding sites is far greater than the level of mutated variants containing only one of the two sites. This result strongly suggests that two HNF-1 molecules bound simultaneously to sites distant from each other can act synergistically to activate gene expression. SN - 0261-4189 UR - https://www.unboundmedicine.com/medline/citation/2265613/Synergistic_trans_activation_of_the_human_C_reactive_protein_promoter_by_transcription_factor_HNF_1_binding_at_two_distinct_sites_ L2 - https://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0261-4189&date=1990&volume=9&issue=13&spage=4467 DB - PRIME DP - Unbound Medicine ER -