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Volume 270,
Number 8,
Issue of February 24, 1995 pp. 3710-3719
©1995 by The American Society for Biochemistry and Molecular Biology, Inc.
Control
of Vascular Cell Adhesion Molecule-1 Gene Promoter Activity during
Neural Differentiation
(Received for publication, June 6,
1994; and in revised form, November 28, 1994)
Allan M.
Sheppard,
Jay
J.
McQuillan,
Michael F.
Iademarco ,
Douglas C.
Dean
Here we demonstrate that vascular cell adhesion molecule-1
(VCAM-1) is expressed in the developing central nervous system on
neuroepithelial cells, which are the precursors of neurons and glia. As
these cells differentiate, VCAM-1 is restricted to a subset of the
glial population. An understanding of mechanisms responsible for this
restricted pattern could provide insights into how lineage-specific
gene expression is maintained during neural differentiation. As a model
of neural differentiation, we turned to the P19 embryonic carcinoma
cell line, which in response to retinoic acid will differentiate along
a neural pathway. We show that VCAM-1 expression on the differentiating
P19 cells resembles that in the central nervous system. Transfection of
VCAM-1 gene promoter constructs into P19 cells revealed that the VCAM-1
gene is controlled sequentially by negative and positive elements
during differentiation. We present evidence that early during
differentiation, POU proteins block VCAM-1 gene activity; however,
later in differentiation coincident with the appearance of VCAM-1 the
pattern of POU proteins changes and the VCAM-1 gene promoter is
activated. This activation is mediated through the NF B/rel complex
p50/p65, which forms during P19 cell differentiation.

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Copyright © 1995 by the American Society for Biochemistry and Molecular Biology.
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