Regulation of α2 integrin gene expression in cells with megakaryocytic features: A common theme of three necessary elements

Abstract

The α2β1 integrin mediates interactions between cells and the extracellular matrix molecules, collagen and/or laminin. The α2β1 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 α2β1 integrin during megakaryocytic differentiation is a consequence of transcriptional activation of the α2 gene. We have begun to characterize the role of the 5' flanking region of the α2 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 α2 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 α2 promoter/enhancer suggests a common theme for megakaryocytic gene regulation shared with other megakaryocyte-specific proteins, including α(IIb) integrin subunit and platelet factor 4.