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ESE-1, an enterocyte-specific Ets transcription factor, regulates MIP-3alpha gene expression in Caco-2 human colonic epithelial cells

Kwon, John H ; Keates, Sarah ; Simeonidis, Simos ; Grall, Franck ; Libermann, Towia A ; Keates, Andrew C

The Journal of biological chemistry, 2003-01, Vol.278 (2), p.875 [Periódico revisado por pares]

United States

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Título:
ESE-1, an enterocyte-specific Ets transcription factor, regulates MIP-3alpha gene expression in Caco-2 human colonic epithelial cells
Autor: Kwon, John H ; Keates, Sarah ; Simeonidis, Simos ; Grall, Franck ; Libermann, Towia A ; Keates, Andrew C
Assuntos: Base Sequence ; Binding Sites ; Caco-2 Cells ; CCAAT-Enhancer-Binding Proteins - metabolism ; Chemokine CCL20 ; Chemokines, CC - genetics ; Cloning, Molecular ; DNA-Binding Proteins - metabolism ; Gene Expression Regulation ; Humans ; Interleukin-1 - pharmacology ; Macrophage Inflammatory Proteins - genetics ; Molecular Sequence Data ; NF-kappa B - metabolism ; Promoter Regions, Genetic ; Proto-Oncogene Proteins ; Proto-Oncogene Proteins c-ets ; Receptors, CCR6 ; Receptors, Chemokine ; Sp1 Transcription Factor - metabolism ; Sp3 Transcription Factor ; Trans-Activators - physiology ; Transcription Factors - metabolism ; Transcription, Genetic ; Transcriptional Activation
É parte de: The Journal of biological chemistry, 2003-01, Vol.278 (2), p.875
Descrição: We have previously shown that colonic epithelial cells are a major site of MIP-3alpha production in human colon and that enterocyte MIP-3alpha protein levels are elevated in inflammatory bowel disease. The aim of this study was to determine the molecular mechanisms regulating MIP-3alpha gene transcription in Caco-2 intestinal epithelial cells. We show that a kappaB element at nucleotides -82 to -93 of the MIP-3alpha promoter binds p50/p65 NF-kappaB heterodimers and is a major regulator of basal and interleukin-1beta (IL-1beta)-mediated gene activation. Scanning mutagenesis of the MIP-3alpha 5'-flanking region also identified two additional binding elements: Site X (nucleotides -63 to -69) and Site Y (nucleotides -143 to -154). Site X (CGCCTTC) bound Sp1 and regulated basal MIP-3alpha gene transcription. Overexpression of Sp1 increased basal luciferase activity, whereas, substitutions in the Sp1 element significantly reduced reporter activity. In contrast, Site Y (AAGCAGGAAGTT) regulated both basal and cytokine-induced gene activation and bound the Ets nuclear factor ESE-1. Substitutions in the Site Y element markedly reduced inducible MIP-3alpha reporter activity. Conversely, overexpression of ESE-1 significantly up-regulated MIP-3alpha luciferase levels. Taken together, our findings demonstrate that co-ordinate activation and binding of ESE-1, Sp1, and NF-kappaB to the MIP-3alpha promoter is required for maximal gene expression by cytokine-stimulated Caco-2 human intestinal epithelial cells.
Editor: United States
Idioma: Inglês

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ESE-1, an enterocyte-specific Ets transcription factor, regulates MIP-3alpha gene expression in Caco-2 human colonic epithelial cells

Kwon, John H ; Keates, Sarah ; Simeonidis, Simos ; Grall, Franck ; Libermann, Towia A ; Keates, Andrew C

United States

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