HMGI(Y) and Sp1 in addition to NF-kappa B regulate transcription of the MGSA/GRO alpha gene.

Wood LD, Farmer AA, Richmond A
Nucleic Acids Res. 1995 23 (20): 4210-9

PMID: 7479086 · PMCID: PMC307364 · DOI:10.1093/nar/23.20.4210

Expression of the chemokine MGSA/GRO is upregulated as melanocytes progress to melanoma cells. We demonstrate that constitutive and cytokine induced MGSA/GRO alpha expression requires multiple DNA regulatory regions between positions -143 to -62. We have previously shown that the NF-kappa B element at -83 to -65 is essential for basal and cytokine induced MGSA/GRO alpha promoter activity in the Hs294T melanoma and normal retinal pigment epithelial (RPE) cells, respectively. Here, we have determined that the Sp1 binding element located approximately 42 base pairs upstream from the NF-kappa B element binds Sp1 and Sp3 constitutively and this element is necessary for basal MGSA/GRO alpha promoter activity. We demonstrate that the high mobility group proteins HMGI(Y) recognize the AT-rich motif nested within the NF-kappa B element in the MGSA/GRO alpha promoter. Loss of either NF-kappa B or HMGI(Y) complex binding by selected point mutations in the NF-kappa B element results in decreased basal and cytokine induced MGSA/GRO alpha promoter activity. Thus, these results indicate that transcriptional regulation of the chemokine MGSA/GRO alpha requires at least three transcription factors: Sp1, NF-kappa B and HMGI(Y).

MeSH Terms (28)

Base Sequence Cells, Cultured Chemokine CXCL1 Chemokines, CXC Chemotactic Factors DNA DNA, Neoplasm DNA-Binding Proteins DNA Footprinting Enhancer Elements, Genetic Gene Expression Regulation Gene Expression Regulation, Neoplastic Growth Substances High Mobility Group Proteins HMGA1a Protein Humans Intercellular Signaling Peptides and Proteins Melanoma Molecular Sequence Data Neoplasm Proteins NF-kappa B Pigment Epithelium of Eye Promoter Regions, Genetic Sp1 Transcription Factor Sp3 Transcription Factor Transcription, Genetic Transcription Factors Tumor Cells, Cultured

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