XXXX site-mediated negative regulation of the @entity2858 promoter by CCAAT/enhancer binding proteins in brain-derived cells.

@entity1 @entity2451 @entity25576 @entity2858 @entity645 @entity1359 @entity4515 @entity463 @entity521 @entity6863
Several transcription regulatory elements that interact with cellular DNA-binding proteins have been identified in the @entity2858 long terminal repeat (LTR). We have identified two sequence motifs in the U3 region of the LTR that are similar to the consensus 9-bp DNA-binding element of the @entity6863 ( @entity6863 ) family of transcription factors. One of the sequences (promoter-proximal) mapped immediately upstream of the @entity2451 element, whereas the other (promoter-distal) completely overlapped the @entity25576 ( @entity25576 ) binding site. In this study, we investigated the role of the enhancer-proximal consensus @entity6863 binding sequence in the expression of the @entity2858 LTR. In cotransfection assays we found that although this sequence is a functional @entity6863 -responsive element, the regulation of the @entity645 promoter by @entity6863 is very complex. @entity6863 isoforms inhibited the @entity1359 ( @entity4515 )-stimulated @entity2858 promoter activity in @entity1 @entity463 @entity1 and @entity521 SHSY5Y cells, but not in HeLa epithelial cells, and this inhibition required the @entity2451 element. @entity6863 also downregulated the @entity645 @entity2451 element-containing SV40 early promoter activity, regardless of the presence of the flanking @entity6863 -binding sequences, in the two brain-derived cells. In electrophoretic mobility shift assays with nuclear extracts from HeLa and @entity1 cells, purified @entity6863 markedly increased the complex formation between endogenous proteins and the @entity2451 DNA probe without detectable association with the complex. However, with extracts from @entity1 cells but not from HeLa cells, a slow migrating complex was observed. Our data suggest that the @entity6863 family of transcription factors can downregulate the @entity2858 promoter activity in CNS-derived cells through the @entity2451 binding elements.
