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Blood, 15 March 2004, Vol. 103, No. 6, pp. 2055-2061.
Prepublished online as a Blood First Edition Paper on November 20, 2003; DOI 10.1182/blood-2003-06-1881.


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Submitted June 11, 2003
Accepted October 13, 2003

Alternative promoters regulate transcription of the gene encoding stem cell surface protein AC133

Sergey V Shmelkov*, Lin Jun, Ryan St. Clair, Deirdre McGarrigle, Christopher A Derderian, Jaroslav K Usenko, Carla Costa, Fan Zhang, Xinzheng Guo, and Shahin Rafii

Department of Medicine, Division of Hematology-Oncology, Weill Medical College of Cornell University, New York, NY, USA

* Corresponding author; email: svs2001{at}med.cornell.edu.

AC133 is a member of a novel family of cell surface proteins with five transmembrane domains. The function of AC133 is unknown. Although AC133 mRNA is detected in different tissues, its expression in the hematopoietic system is restricted to CD34+ stem cells. AC133 is also expressed on stem cells of other tissues, including endothelial progenitor cells. However, despite the potential importance of AC133 to the field of stem cell biology, nothing is known about the transcriptional regulation of AC133 expression. In this report we showed that the human AC133 gene has at least nine distinctive 5'-UTR exons, resulting in the formation of at least seven alternatively spliced 5'-UTR isoforms of AC133 mRNA, which are expressed in a tissue dependent manner. We found that transcription of these AC133 isoforms is controlled by five alternative promoters, and we demonstrated their activity on AC133 expressing cell lines using a luciferase reporter system. We also showed that in vitro methylation of two of these AC133 promoters completely suppresses their activity, suggesting that methylation plays a role in their regulation. Identification of tissue specific AC133 promoters may provide a novel method to isolate tissue-specific stem and progenitor cells.


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