HMGI(Y) and Sp1 in addition to nf-κb regulate transcription of the MGSA/GROα gene

Abstract

Expression of the chemokine MGSA/GRO is upregulated as melanocytes progress to melanoma cells. We demonstrate that constitutive and cytokine induced MGSA/GROα expression requires multiple DNA regulatory regions between positions -143 to -62. We have previously shown that the NF-KB element at -83 to -65 is essential for basal and cytokine induced MGSA/GROα promoter activity in the Hs294T melanoma and normal retinal pigment epithelial (RPE) cells, respectively. Here, we have determined that the Spl binding element located -42 base pairs upstream from the NF-κB element binds Sp1 and Sp3 constitutively and this element is necessary for basal MGSA/GROα promoter activity. We demonstrate that the high mobility group proteins HMGI(Y) recognize the AT-rich motif nested within the NF-κB element in the MGSA/GROα promoter. Loss of either NF-κB or HMGI(Y) complex binding by selected point mutations in the NF-κB element results in decreased basal and cytokine induced MGSA/GROα promoter activity. Thus, these results indicate that transcriptional regulation of the chemokine MGSA/GROα requires at least three transcription factors: Sp1, NF-κB and HMGI(Y). © 1995, Oxford University Press.