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

• Published in: Blood Vol. 103; no. 6; pp. 2055 - 2061
• Main Authors: Shmelkov, Sergey V., Jun, Lin, St Clair, Ryan, McGarrigle, Deirdre, Derderian, Christopher A., Usenko, Jaroslav K., Costa, Carla, Zhang, Fan, Guo, Xinzheng, Rafii, Shahin
• Format: Journal Article
• Language: English
• Published: Washington, DC Elsevier Inc 15.03.2004; The Americain Society of Hematology
• Subjects: 5' Untranslated Regions - genetics; AC133 Antigen; Alternative Splicing - physiology; Antigens, CD; Base Sequence; Biological and medical sciences; Caco-2 Cells; Cell differentiation, maturation, development, hematopoiesis; Cell physiology; Cell Separation - methods; Cloning, Molecular; DNA Methylation; Fetal Blood - cytology; Fundamental and applied biological sciences. Psychology; Gene Expression; Glycoproteins - genetics; Hematopoietic Stem Cells - cytology; Hematopoietic Stem Cells - physiology; Humans; Molecular and cellular biology; Molecular Sequence Data; Peptides - genetics; Promoter Regions, Genetic - genetics; Retinoblastoma; Teratocarcinoma; Transcription Initiation Site; Transcription, Genetic - genetics; Transmembrane protein; Regulation(control); Gene; Transcription; Transcription promoter; Stem cell; Protein AC133; Hematopoietic cell; Cell surface; Protein
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2003-06-1881

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.