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International Journal of Fertility and Sterility، جلد ۸، شماره ۲.۵، صفحات ۱۶۸-۱۶۸
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عنوان انگلیسی P-157: Polymorphic Core Promoter GA-repeats Alter Gene Expression of The Early Embryonic Developmental Genes
چکیده انگلیسی مقاله Background: We examine the GA-repeat core promoters of MECOM and GABRA3 in human embryonic kidney-293 cell line and show that those GA-repeats have promoter activity,and those different alleles of the repeats can significantly alter gene expression.We propose a novel role for GA-repeat core promoters to regulate gene expression in the genes involved in development and evolution. Materials and Methods: The core promoter sequence of human MECOM and GABRA3 genes was amplified by PCR. Three different alleles ranging the longest, medium, and shortest allele size were selected followed by sequencing,and were used for cloning and expression studies.The fragments cloned into pGL3 basic luciferase vector and transfected into HEK-293 cells.24h after transfection,luciferase activities was measured. Results: The MECOM and GABRA3 core promoter GA-repeats are polymorphic in humans and We detected significant difference in gene expression activity as a result of different alleles across MECOM and GABRA3 core promoters in the HEK-293 cell line. Conclusion: 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.We have previously identified human protein coding gene core promoters that are composed of exceptionally long GArepeats. 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 analyzed the functional implication of GA repeats in the core promoter of two additional genes, MECOM and GABRA3,whose expression is largely limited to embryogenesis. Similar to the SOX5 gene,MECOM and GABRA3 are involved in key developmental processes.Null mutations within the SOX5 and MECOM genes are lethal in the embryo,whereas hemizogosity for the GABRA3 deleterious mutations result in disorders within the brain. Across-species homology check revealed that the GA-repeats in the core promoters of the three genes,SOX5,MECOM,and GABRA3 are highly conserved across evolution,which further strengthens a role for those repeats in gene expression and evolution.
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نشانی اینترنتی http://ijfs.ir/journal/article/abstract/4019
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