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Publication : Functional analysis of the endothelial cell-specific Tie2/Tek promoter identifies unique protein-binding elements.

First Author  Fadel BM Year  1998
Journal  Biochem J Volume  330 ( Pt 1)
Pages  335-43 PubMed ID  9461528
Mgi Jnum  J:46290 Mgi Id  MGI:1197459
Doi  10.1042/bj3300335 Citation  Fadel BM, et al. (1998) Functional analysis of the endothelial cell-specific Tie2/Tek promoter identifies unique protein-binding elements. Biochem J 330(Pt 1):335-43
abstractText  To investigate the molecular basis of endothelial cell-specific gene expression, we have examined the DNA sequences and the cognate DNA-binding proteins that mediate transcription of the murine tie2/tek gene. Reporter transfection experiments conformed with earlier findings in transgenic mice, indicating that the upstream promoter of Tie2/Tek is capable of activating transcription in an endothelial cell-specific fashion. These experiments have also allowed the identification of a single upstream inhibitory region (region I) and two positive regulatory regions (regions U and A) in the proximal promoter. Electrophoretic mobility-shift assays have allowed further characterization of three novel DNA-binding sequences associated with these regions and have provided preliminary characterization of the protein factors binding to these elements. Two of the elements (U and A) confer increased transcription on a heterologous promoter, with element U functioning in an endothelial-cell-selective manner. By employing embryonic endothelial-like yolk sac cells in parallel with adult-derived endothelial cells, we have identified differences in functional activity and protein binding that may reflect mechanisms for specifying developmental regulation of tie2/tek expression. Further study of the DNA and protein elements characterized in these experiments is likely to provide new insight into the molecular basis of developmental- and cell-specific gene expression in the endothelium.
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