Mary Zutter
Faculty Member
Last active: 4/26/2016

Regulation of alpha 2 integrin gene expression in cells with megakaryocytic features: a common theme of three necessary elements.

Zutter MM, Painter AA, Staatz WD, Tsung YL
Blood. 1995 86 (8): 3006-14

PMID: 7579393

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.

MeSH Terms (16)

Antigens, CD Burkitt Lymphoma Dimethyl Sulfoxide Enhancer Elements, Genetic Gene Expression Regulation, Leukemic Genes Humans Integrin alpha2 Integrins Leukemia, Megakaryoblastic, Acute Leukemia, Myelogenous, Chronic, BCR-ABL Positive Megakaryocytes Neoplasm Proteins Phorbol 12,13-Dibutyrate Receptors, Collagen Tumor Cells, Cultured

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