Our previous studies have shown that @entity46999 , a SH2 domain-containing protein- @entity669 phosphatase, is expressed not only in cells of hematopoietic lineages, but also in many non-hematopoietic cells under the control of an alternative tissue-specific promoter, P1. In this study, the activity of the P1 promoter was analyzed in a region spanning 3.5 kb upstream of the major transcription start site in non-hematopoietic MCF-7 cells. Using DNA footprinting, gel retardation assays and mutational analysis, we have characterized cis-regulatory elements that are essential to confer the P1 promoter activity. An upstream @entity3419 element (-126 to -118) positively regulated this TATA-box-lacking promoter. Two inverted CCAAT-elements (-332 to -328 and -66 to -62) played important roles in regulating the @entity46999 gene expression, and transcription factor NF-Y predominantly bound to the two CCAAT-elements. Binding of NF-Y to the distal CCAAT-element enhanced the transcriptional activity of the P1 promoter. In contrast, binding of NF-Y to the proximal CCAAT-element and interacting with repressor(s) inhibited the promoter activity. Furthermore, incubation of MCF7 cells with 100 ng/ml @entity3996 , an inhibitor of histone deacetylase, significantly increased the activity of the P1 promoter. Mutation in the proximal CCAAT-element, however, eliminated the activating effect of @entity3996 on the promoter. Together, our data suggest that NF-Y factor can function either as a specific positive or negative regulator of P1 promoter activity in non-hematopoietic MCF7 cells.

Transcriptional activity of the XXXX gene in MCF7 cells is differentially regulated by binding of NF-Y factor to two distinct CCAAT-elements.

@entity3996 :: ('MESH:C012589', 'Chemical') :: ['trichostatin A'] @entity46999 :: ('5777', 'Gene') :: ['SHP-1'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity3419 :: ('6667', 'Gene') :: ['Sp1']
@entity46999 :: (5777,Gene) :: ['SHP-1']
