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A composite C/EBP binding site is essential for the activity of the promoter of the IL-3/IL-5/granulocyte-macrophage colony-stimulating factor receptor beta c gene.
J Immunol. 1999 Sep 01; 163(5):2674-80.JI

Abstract

The common beta-chain (beta c) is the main signaling component of the heterodimeric receptors for IL-3, IL-5, and GM-CSF and is primarily expressed on myeloid cells. The proximal beta c promoter is regulated by GGAA binding proteins, including PU.1, a hemopoietic specific member of the Ets family. However, it is not likely that PU.1 alone accounts for the myeloid-restricted expression of the beta c subunit. Here we describe the identification of a C/EBP binding enhancer that is located 2 kb upstream of the transcription start site. The enhancer contains two elements that bind C/EBP alpha and -beta in U937 cells, while C/EBP epsilon is also bound in extracts of HL-60 cells. Importantly, deletion of the enhancer or mutation of either of one of the C/EBP sites results in a complete loss of promoter activity in cell lines as well as in primary cells, showing the importance of C/EBP members in beta c gene activation. We further show that PU.1 has to cooperate with C/EBP proteins to induce beta c transcription. Since the beta c is already expressed on CD34+ cells, these results demonstrate that both C/EBP and PU.1 are not only important for the myeloid-specific gene regulation at later stages of myeloid differentiation.

Authors+Show Affiliations

Department of Pulmonary Diseases, University Hospital Utrecht, The Netherlands.No affiliation info availableNo 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

10453008

Citation

van Dijk, T B., et al. "A Composite C/EBP Binding Site Is Essential for the Activity of the Promoter of the IL-3/IL-5/granulocyte-macrophage Colony-stimulating Factor Receptor Beta C Gene." Journal of Immunology (Baltimore, Md. : 1950), vol. 163, no. 5, 1999, pp. 2674-80.
van Dijk TB, Baltus B, Raaijmakers JA, et al. A composite C/EBP binding site is essential for the activity of the promoter of the IL-3/IL-5/granulocyte-macrophage colony-stimulating factor receptor beta c gene. J Immunol. 1999;163(5):2674-80.
van Dijk, T. B., Baltus, B., Raaijmakers, J. A., Lammers, J. W., Koenderman, L., & de Groot, R. P. (1999). A composite C/EBP binding site is essential for the activity of the promoter of the IL-3/IL-5/granulocyte-macrophage colony-stimulating factor receptor beta c gene. Journal of Immunology (Baltimore, Md. : 1950), 163(5), 2674-80.
van Dijk TB, et al. A Composite C/EBP Binding Site Is Essential for the Activity of the Promoter of the IL-3/IL-5/granulocyte-macrophage Colony-stimulating Factor Receptor Beta C Gene. J Immunol. 1999 Sep 1;163(5):2674-80. PubMed PMID: 10453008.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A composite C/EBP binding site is essential for the activity of the promoter of the IL-3/IL-5/granulocyte-macrophage colony-stimulating factor receptor beta c gene. AU - van Dijk,T B, AU - Baltus,B, AU - Raaijmakers,J A, AU - Lammers,J W, AU - Koenderman,L, AU - de Groot,R P, PY - 1999/8/24/pubmed PY - 1999/8/24/medline PY - 1999/8/24/entrez SP - 2674 EP - 80 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J Immunol VL - 163 IS - 5 N2 - The common beta-chain (beta c) is the main signaling component of the heterodimeric receptors for IL-3, IL-5, and GM-CSF and is primarily expressed on myeloid cells. The proximal beta c promoter is regulated by GGAA binding proteins, including PU.1, a hemopoietic specific member of the Ets family. However, it is not likely that PU.1 alone accounts for the myeloid-restricted expression of the beta c subunit. Here we describe the identification of a C/EBP binding enhancer that is located 2 kb upstream of the transcription start site. The enhancer contains two elements that bind C/EBP alpha and -beta in U937 cells, while C/EBP epsilon is also bound in extracts of HL-60 cells. Importantly, deletion of the enhancer or mutation of either of one of the C/EBP sites results in a complete loss of promoter activity in cell lines as well as in primary cells, showing the importance of C/EBP members in beta c gene activation. We further show that PU.1 has to cooperate with C/EBP proteins to induce beta c transcription. Since the beta c is already expressed on CD34+ cells, these results demonstrate that both C/EBP and PU.1 are not only important for the myeloid-specific gene regulation at later stages of myeloid differentiation. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/10453008/A_composite_C/EBP_binding_site_is_essential_for_the_activity_of_the_promoter_of_the_IL_3/IL_5/granulocyte_macrophage_colony_stimulating_factor_receptor_beta_c_gene_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=10453008 DB - PRIME DP - Unbound Medicine ER -