Polymorphic core promoter GA-repeats alter gene expression of the early embryonic developmental genes.
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 that are composed of exceptionally long GA-repeats. The functional implication of those GA-repeats is beginning to emerge in the 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, MECOM and GABRA3, whose expression is largely limited to embryogenesis. We report a 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<1 × 10(-8)). The MECOM core promoter 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.
Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran.
E
E
Valipour
A
A
Kowsari
H
H
Bayat
M
M
Banan
S
S
Kazeminasab
S
S
Mohammadparast
M
M
Ohadi
D000818:Animals; D015331:Cohort Studies; D017124:Conserved Sequence; D004268:DNA-Binding Proteins / Q000235:genetics*; D018900:Dinucleotide Repeats / Q000235:genetics / Q000502:physiology; D019143:Evolution, Molecular; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D005787:Gene Frequency; D050437:Genes, Developmental / Q000235:genetics; D057809:HEK293 Cells; D006801:Humans; D007492:Iran; D000074008:MDS1 and EVI1 Complex Locus Protein; D051379:Mice; D011110:Polymorphism, Genetic / Q000502:physiology*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D011519:Proto-Oncogenes / Q000235:genetics*; D011963:Receptors, GABA-A / Q000235:genetics*; D017385:Sequence Homology; D014157:Transcription Factors / Q000235:genetics*
D004268:DNA-Binding Proteins; C546257:GABRA3 protein, human; D000074008:MDS1 and EVI1 Complex Locus Protein; C063575:MECOM protein, human; D011963:Receptors, GABA-A; D014157:Transcription Factors
Core promoter; Expression; GA-repeat; GABRA3; GAMMA-AMINOBUTYRIC ACID RECEPTOR, ALPHA-3; INR; Initiator motif; MDS1 and MECOM complex locus; MECOM; STR; Short Tandem Repeat; TSS; Transcription Start Site; UTR; Untranslated Region