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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. This Article Full Text Full Text (PDF) All Versions of this Article: 2003-06-1881v1 103/6/2055    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Shmelkov, S. V. Articles by Rafii, S. Search for Related Content PubMed PubMed Citation Articles by Shmelkov, S. V. Articles by Rafii, S. Related Collections Hematopoiesis and Stem Cells Gene Expression Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMATOPOIESIS Alternative promoters regulate transcription of the gene that encodes 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 From the Weill Medical College of Cornell University, Division of Hematology-Oncology, New York, NY. AC133 is a member of a novel family of cell surface proteins with 5 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 9 distinctive 5'–untranslated region (UTR) exons, resulting in the formation of at least 7 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 5 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 2 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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