title: Transcriptional regulation of the human mitochondrial peptide deformylase (PDF).
abstract: The last years of research have been particularly dynamic in establishing the importance of peptide deformylase (PDF), a protein of the N-terminal methionine excision (NME) pathway that removes formyl-methionine from mitochondrial-encoded proteins. The genomic sequence of the human PDF gene is shared with the COG8 gene, which encodes a component of the oligomeric golgi complex, a very unusual case in Eukaryotic genomes. Since PDF is crucial in maintaining mitochondrial function and given the atypical short distance between the end of COG8 coding sequence and the PDF initiation codon, we investigated whether the regulation of the human PDF is affected by the COG8 overlapping partner. Our data reveals that PDF has several transcription start sites, the most important of which only 18 bp from the initiation codon. Furthermore, luciferase-activation assays using differently-sized fragments defined a 97 bp minimal promoter region for human PDF, which is capable of very strong transcriptional activity. This fragment contains a potential Sp1 binding site highly conserved in mammalian species. We show that this binding site, whose mutation significantly reduces transcription activation, is a target for the Sp1 transcription factor, and possibly of other members of the Sp family. Importantly, the entire minimal promoter region is located after the end of COG8's coding region, strongly suggesting that the human PDF preserves an independent regulation from its overlapping partner.
authors.affiliation: IPATIMUP-Institute of Molecular Pathology and Immunology of University of Porto, Portugal. isabelpereiracastro@gmail.com
authors.forename: Isabel
authors.initials: I
authors.lastname: Pereira-Castro
authors.forename: Luís Teixeira da
authors.initials: LT
authors.lastname: Costa
authors.forename: António
authors.initials: A
authors.lastname: Amorim
authors.forename: Luisa
authors.initials: L
authors.lastname: Azevedo
mesh_terms: D020121:5' Untranslated Regions / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics; D000581:Amidohydrolases / Q000235:genetics*; D001483:Base Sequence; D017124:Conserved Sequence; D015971:Gene Expression Regulation, Enzymologic; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008928:Mitochondria / Q000201:enzymology*; D011401:Promoter Regions, Genetic; D016329:Sp1 Transcription Factor / Q000378:metabolism; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
chemical_list: D020121:5' Untranslated Regions; D033942:Adaptor Proteins, Vesicular Transport; C522290:COG8 protein, human; D016329:Sp1 Transcription Factor; D008156:Luciferases; D000581:Amidohydrolases; C084507:peptide deformylase