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Regulation of the human transforming growth factor β type II receptor gene promoter by novel Sp1 sites

Abstract

The transforming growth factor-β (TGFβ) type II receptor (TβR-II) is responsible for transducing the growth inhibitory signals of TGFβ. The TβR-II gene promoter lacks both a TATA box and a CAAT box near the transcription initiation site, and has been shown to contain binding sequences for several transcription factors (Sp1, AP1, NF-Y, Cut and ERT) which are important for TβR-II gene promoter activity in vitro. However, it is still not clear which interactions are important for the regulation of TβR-II gene promoter activity in vivo. Using in vivo genomic DNA footprinting of normal human epithelial cells (HaCaT), we have identified two novel identical and strongly protected sites (ggggctgg) at positions −59 and −102 of the TβR-II gene promoter. Mutation of either site significantly reduced promoter activity in transient transfections. Protein binding to these sites, as determined by electrophoretic mobility shift assays (EMSA), was specifically competed with consensus Sp1 oligonucleotides. Furthermore, anti-Sp1/3 antibodies produced band shifts when incubated with the TβR-II −59 and −102 DNA probes. Importantly, Sp1 protein binding was influenced by the presence of an intact NF-Y binding site at position −83. Our data suggests that both Sp1 and NF-Y may play an important role in regulating TβR-II gene promoter basal activity in vivo.

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Acknowledgements

We would like to thank Dr Nancy Olashaw for critically reading this manuscript. This study was partially supported by the American Cancer Society Grant #RPG-98-039-01-CNE.

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Correspondence to Kenneth L Wright.

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Jennings, R., Alsarraj, M., Wright, K. et al. Regulation of the human transforming growth factor β type II receptor gene promoter by novel Sp1 sites. Oncogene 20, 6899–6909 (2001). https://doi.org/10.1038/sj.onc.1204808

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