Regulation of the human MSH6 gene by the Sp1 transcription factor and alteration of promoter activity and expression by polymorphisms.

ABSTRACT: Defects in human DNA mismatch repair have been reported to underlie a variety of hereditary and sporadic cancer cases. We characterized the structure of the MSH6 promoter region to examine the mechanisms of transcriptional regulation of the MSH6 gene. The 5'-flanking region of the MSH6 gene was found to contain seven functional Sp1 transcription factor binding sites that each bind Sp1 and Sp3 and contribute to promoter activity. Transcription did not appear to require a TATA box and resulted in multiple start sites, including two major start sites and at least nine minor start sites. Three common polymorphisms were identified in the promoter region (-557 T-->G, -448 G-->A, and -159 C-->T): the latter two were always associated, and each of these functionally inactivated a different Sp1 sit

SUBMITTER: Gazzoli I 

PROVIDER: S-EPMC262342 | biostudies-literature | 2003 Nov

REPOSITORIES: biostudies-literature