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Regulation of alpha 2 integrin gene expression in cells with megakaryocytic
features: a common theme of three necessary elements
MM Zutter, AA Painter, WD Staatz and YL Tsung
Department of Pathology, Washington University School of Medicine, St.
Louis, MO 63110, USA.
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.
Volume 86,
Issue 8,
pp. 3006-3014,
10/15/1995
Copyright © 1995 by The American Society of Hematology
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