Transcriptional activity of the SHP-1 gene in MCF7 cells is differentially regulated by binding of NF-Y factor to two distinct CCAAT-elements

被引:30
作者
Xu, Y
Banville, D
Zhao, HF
Zhao, X
Shen, SH
机构
[1] McGill Univ, Dept Anim Sci, St Anne De Bellevue, PQ H9X 3V9, Canada
[2] Natl Res Council Canada, Biotechnol Res Inst, Montreal, PQ H4P 2R2, Canada
[3] McGill Univ, Dept Med, Montreal, PQ H3G 1A4, Canada
关键词
protein-tyrosine phosphatase; promoter; transcription factors; histone deacetylase;
D O I
10.1016/S0378-1119(01)00445-0
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Our previous studies have shown that SHP-1, a SH2 domain-containing protein-tyrosine 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, pi. 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 nonhematopoietic MCF-7 cells. Using DNA footprinting, gel retardation assays and mutational analysis, we have characterized cis-regulatory elements that are essential to confer the pi promoter activity. An upstream Spl 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 SHP-1 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 trichostatin A, 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 trichostatin A 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. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:141 / 153
页数:13
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