Control of vascular cell adhesion molecule-1 gene promoter activity during neural differentiation.
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 kappa B/rel complex p50/p65, which forms during P19 cell differentiation.
Sheppard
A M
AM
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri 63110.
McQuillan
J J
JJ
Iademarco
M F
MF
Dean
D C
DC
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D002490:Central Nervous System / Q000166:cytology* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D051379:Mice; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D014411:Neoplastic Stem Cells; D050809:POU Domain Factors; D011247:Pregnancy; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051841:Transcription Factor RelB; D014157:Transcription Factors / Q000378:metabolism; D019010:Vascular Cell Adhesion Molecule-1
D015815:Cell Adhesion Molecules; D004268:DNA-Binding Proteins; D016328:NF-kappa B; D050809:POU Domain Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; C497594:Relb protein, mouse; D014157:Transcription Factors; D019010:Vascular Cell Adhesion Molecule-1; D051841:Transcription Factor RelB