Usage of Polymorphic GA-Repeat Core Promoters in Evolution and Development

Protein complexes that bind to 'GAGA' DNA elements are necessary to replace nucleosomes to create a local chromatin environment that facilitates a variety of site-specific regulatory responses. Three to four elements are required for the disruption of a preassembled nucleosome. We have previously identified human protein-coding gene core promoters thatare composed of exceptionally long GA-repeats. The functional implication of those GA-repeats is beginning to emerge inthe core promoter of the human SOX5 gene, which is involved in multiple developmental processes. In the current study,we analyze the functional implication of GA-repeats in the core promoter of two additional genes, EVI1 and GABRA3,whose expression is largely limited to embryogenesis. We report significant difference in gene expression as a result of different alleles across those core promoters in the HEK-293 cell line. Across-species homology check for the GABRA3 GA-repeats revealed that those repeats are evolutionary conserved in mouse and primates (p<1x10-8). The EVI1 corepromoter GA-repeats are also conserved in numerous species, of which human has the longest repeat and complexity. We propose a novel role for GA-repeat core promoters to regulate gene expression in the genes involved in development and evolution

Keywords:

EVI1 , GABRA3 , short tandem repeat , core promoter , expression