title: Alternative promoters regulate transcription of the gene that encodes stem cell surface protein AC133.
abstract: 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.
authors: Weill Medical College of Cornell University, Division of Hematology-Oncology, 1300 York Ave, MED/HEM/ONC, C-606, New York, NY 10021, USA. svs2001@med.cornell.edu
authors: Sergey V
authors: SV
authors: Shmelkov
authors: Lin
authors: L
authors: Jun
authors: Ryan
authors: R
authors: St Clair
authors: Deirdre
authors: D
authors: McGarrigle
authors: Christopher A
authors: CA
authors: Derderian
authors: Jaroslav K
authors: JK
authors: Usenko
authors: Carla
authors: C
authors: Costa
authors: Fan
authors: F
authors: Zhang
authors: Xinzheng
authors: X
authors: Guo
authors: Shahin
authors: S
authors: Rafii
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D000071916:AC133 Antigen; D017398:Alternative Splicing / Q000502:physiology; D015703:Antigens, CD; D001483:Base Sequence; D018938:Caco-2 Cells; D002469:Cell Separation / Q000379:methods; D003001:Cloning, Molecular; D019175:DNA Methylation; D005312:Fetal Blood / Q000166:cytology; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012175:Retinoblastoma; D018243:Teratocarcinoma; D024363:Transcription Initiation Site; D014158:Transcription, Genetic / Q000235:genetics*
chemical_list: D020121:5' Untranslated Regions; D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides