Human HMGA2 promoter is coregulated by a polymorphic dinucleotide (TC)-repeat

Abstract

HMGA proteins are thought to be causally involved in the progression of different diseases, including benign and malignant tumors, obesity, arteriosclerosis, and restenosis. As HMGA proteins are architectural transcription factors, their binding to DNA leads to changes in DNA-conformation modulating the environment for the assembly and function of transcriptional complexes, thus influencing the expression of a huge variety of genes. Despite the emerging role of HMGA proteins for important diseases, only limited information is available about mechanisms regulating the expression of the HMGA2 gene. In this report, 2240 bp of the 5' flanking region of the HMGA2 gene were functionally analyzed by luciferase assay experiments. Besides the identification of novel positive and negative regulatory elements, it was shown that transcription is initiated from two independent promoter regions within cell lines HeLa, MCF7, and L14TSV40. Furthermore, a functional polymorphic dinucleotide repeat (TCTCT(TC)(n)) 500 bp upstream of the ATG translational start codon was found to regulate strongly the human HMGA2 promoter with an activation pattern that correlates to its TC-repeat length.