Murine H-rev107 gene encoding a class II tumor suppressor: gene organization and identification of an Sp1/Sp3-binding GC-box required for its transcription.

Abstract:

:H-rev107, which belongs to class II tumor suppressor genes, is ubiquitously expressed in normal cells, but is downregulated in many carcinomas and tumor cell lines. Sequence analysis showed that the murine H-rev107 gene is composed of five exons and four introns. Transfections revealed that 7.6 kb of the H-rev107 promoter directed a high level expression of the reporter gene. There were no significant differences in promoter activity when various 5'-deletion promoter constructs from -7.6 kb to -113 bp were employed. By further deletion and mutation analysis, we found that the region between -83 and -75 containing a GC-box was essential for promoter activity in NIH3T3 or REF52 fibroblasts expressing H-rev107 at moderate to high levels. Gelshifts demonstrated in vitro binding of Sp1 and Sp3 to this GC-box. Cotransfection of Sp1 and Sp3 functionally stimulated promoter activity in SL2 cells. By chromatin immunoprecipitation assays, we observed in vivo binding of Sp1 and Sp3 to the proximal promoter region in NIH3T3 cells and liver, concluding that the transcription of the H-rev107 gene is dependent on Sp1/Sp3-binding to the -83/-75 GC-box.

authors

Roder K,Latasa MJ,Sul HS

doi

10.1016/S0006-291X(02)00274-7

subject

Has Abstract

pub_date

2002-05-03 00:00:00

pages

793-9

issue

2

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(02)00274-7

journal_volume

293

pub_type

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