Single strand DNA-binding proteins and XXXX conjointly regulate thyrotropin receptor gene expression.

@entity268 @entity1880 @entity10344 @entity45484 @entity44935 @entity35 @entity45880 @entity1928
An element, -186 to -176 base pairs (bp), in the minimal @entity44935 ( @entity44935 ) promoter binds @entity45880 ( @entity45880 ) and is important for both constitutive expression and TSH/ @entity268 -induced negative autoregulation of the @entity44935 in thyroid cells. An element on the noncoding strand of the @entity44935 , contiguous with the 5'-end of the @entity45880 element, has single strand binding activity. It is distinct from the @entity45880 site, as evidenced by competition experiments using gel shift assays; but the association of the two elements is not random. Thus, the @entity45484 ( @entity45484 ) element also exists contiguous to the 5'-end of an upstream @entity45880 site, -881 to -866 bp; mutation of two conserved nucleotides in each @entity45484 element results in the loss of @entity45484 binding and cross-competition. Transfection experiments indicate that full, constitutive @entity44935 gene expression in @entity35 thyroid cells requires the binding of both SSBPs and @entity45880 , since mutation of either element halves thyroid-specific promoter activity, whereas mutation of both decreases promoter activity to values near those of a control vector. Transfection experiments with @entity35 liver cells support their independent activities and show that the @entity45484 site contributes to @entity44935 gene expression in non-thyroid tissue. The SSBPs function conjointly with @entity45880 in thyroid-specific, TSH/ @entity268 -induced negative autoregulation of the @entity44935 . Thus, @entity10344 or @entity1928 -treated @entity35 cells coordinately decrease @entity44935 RNA levels and @entity44935 DNA binding to both the SSBPs and @entity45880 ; also the maximal TSH/ @entity268 -induced decrease in gene expression requires both elements. The TSH-induced effect in each case is inhibited by @entity1880 ; the TSH-induced decrease in @entity45484 /DNA complex formation requires the presence of insulin or calf serum, exactly as does TSH-induced down-regulation of @entity44935 RNA levels. In sum, full, constitutive expression of the @entity44935 in thyroid cells requires @entity45880 and the SSBPs to bind separate, contiguous elements on the @entity44935 promoter. TSH/ @entity268 decreases the binding of each factor to its respective site, thereby decreasing @entity44935 gene expression. The role of the @entity45484 and @entity45880 sites in constitutive @entity44935 expression and in TSH/ @entity268 -induced negative regulation of the @entity44935 is, therefore, additive and independent.
