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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 NFkappaB/rel complex p50/p65, which forms during P19 cell differentiation.




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