title: Regulation of alpha 2 integrin gene expression in cells with megakaryocytic features: a common theme of three necessary elements.
abstract: The alpha 2 beta 1 integrin mediates interactions between cells and the extracellular matrix molecules, collagen and/or laminin. The alpha 2 beta 1 integrin is expressed in a variety of cell types, but in cells of hematopoietic lineage, expression is restricted to megakaryocytes and platelets. Increased expression of the alpha 2 beta 1 integrin during megakaryocytic differentiation is a consequence of transcriptional activation of the alpha 2 gene. We have begun to characterize the role of the 5' flanking region of the alpha 2 integrin gene in regulating expression during megakaryocyte differentiation. A 5-kb fragment of the 5' region directs both cell type and differentiation-dependent expression of a reporter gene in the pluripotent hematopoietic K562 cells upon megakaryocytic differentiation and in the megakaryocytic cell line, Dami. Analysis of a series of 5' deletion mutants indicates that expression of the alpha 2 integrin gene in cells with megakaryocytic features requires a core promoter region, a silencer region, and megakaryocytic enhancers in the distal 5' end. The organization of these three distinct regulatory regions of the alpha 2 promoter/enhancer suggests a common theme for megakaryocytic gene regulation shared with other megakaryocyte-specific proteins, including alpha IIb integrin subunit and platelet factor 4.
authors.affiliation: Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Zutter
authors.forename: A A
authors.initials: AA
authors.lastname: Painter
authors.forename: W D
authors.initials: WD
authors.lastname: Staatz
authors.forename: Y L
authors.initials: YL
authors.lastname: Tsung
mesh_terms: D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics; D002051:Burkitt Lymphoma / Q000473:pathology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004742:Enhancer Elements, Genetic; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D005796:Genes; D006801:Humans; D039421:Integrin alpha2; D016023:Integrins / Q000378:metabolism; D007947:Leukemia, Megakaryoblastic, Acute / Q000473:pathology; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000473:pathology; D008533:Megakaryocytes / Q000187:drug effects*; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D038981:Receptors, Collagen; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D015703:Antigens, CD; D039421:Integrin alpha2; D016023:Integrins; D009363:Neoplasm Proteins; D038981:Receptors, Collagen; D015240:Phorbol 12,13-Dibutyrate; D004121:Dimethyl Sulfoxide