Characterization of the rat cytoplasmic C1-tetrahydrofolate synthase gene and analysis of its expression in liver regeneration and fetal development

作者: Katherine M Howard , Stephanie J Muga , Liwen Zhang , Anice E Thigpen , Dean R Appling

DOI: 10.1016/S0378-1119(03)00796-0

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摘要: Abstract The eukaryotic trifunctional enzyme, C1-tetrahydrofolate (THF) synthase, interconverts folic acid derivatives between various oxidation states and is critical for normal cellular function, growth, differentiation. Using a rat C1-THF synthase cDNA synthetic oligonucleotides, the gene was isolated characterized. consists of 28 exons spans 67.5 kbp. Primer extension, RNase protection, rapid amplification ends (RACE) experiments indicate presence multiple transcription start points (tsp) within 250-bp window located 50 300 bp upstream from codon. 5′ flanking region devoid TATA consensus sequence motif, but putative regulatory elements, including NF-κβ, HNF-4α1, RARα1, C/EBP, PPAR are present in promoter region. also contains two sets tetranucleotide repeats short interspersed nuclear elements (SINES). initial 2500 sequences mouse cytoplasmic genes share 70% identity. However, comparison with human Human Genome Data Bank revealed no significant homology structure characterization led to identification pseudogene that 94% identical probably diverged 10–12 million years ago. In addition, expression patterns were investigated during liver regeneration kidney organogenesis, highly regulated events. both processes, correlated increased nucleotide metabolism. This pattern suggests response changes demand folate-dependent one-carbon units.

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