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The human promyelocytic leukemia zinc finger gene is regulated by the Evi-1 oncoprotein and a novel guanine-rich site binding protein

Leukemia volume 16, pages 1755–1762 (2002)Cite this article

Abstract

PLZF (promyelocytic leukemia zinc finger) is a transcription factor disrupted in t(11;17)-associated acute promyelocytic leukemia which is highly expressed in undifferentiated myeloid cells. To address the tissue-specific regulation of the promoter, we isolated sequences 1.2-kb 5′ to the transcriptional start site. Sequence analysis demonstrated that this region contains one TATA box and several putative transcription factor binding sites including four G/C-rich sites and one Evi-1-like site. A fragment of the promoter spanning 158-bp upstream of the transcription start site displayed relative specificity for PLZF-expressing myeloid cells. Functional promoter assays revealed that an Evi-1-like site at −140/−130 was essential for full promoter activity in every cell line tested while a G-rich site at −15/−7 was important for tissue specificity. Electrophoretic mobility shift assays showed that Evi-1 binds specifically to −140/−130 Evi-1-like site and overexpression of Evi-1 in K562 cells activated the PLZF promoter. UV cross-linking assays showed that the proximal, tissue specific element at −15/−7 bound a novel 28 kDa protein. These results indicate as with other myeloid genes, a relatively small segment of DNA can direct tissue-specific expression, but unlike other myeloid promoters, no critical PU.1 or C/EBP sites were found.

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Acknowledgements

Supported by NIH Grant CA59936 and American Cancer Society Grant DHP 160.

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  1. Department of Medicine and Derald H Ruttenberg Cancer Center, The Mount Sinai School of Medicine, New York, NY, USA

    S Takahashi & JD Licht

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Takahashi, S., Licht, J. The human promyelocytic leukemia zinc finger gene is regulated by the Evi-1 oncoprotein and a novel guanine-rich site binding protein. Leukemia 16, 1755–1762 (2002). https://doi.org/10.1038/sj.leu.2402682

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