title: Computational analysis of the transcriptional regulation of the adenine nucleotide translocator isoform 4 gene and its role in spermatozoid glycolytic metabolism.
abstract: Computational phylogenetic analysis coupled to promoter sequence alignment was used to understand mechanisms of transcriptional regulation and to identify potentially coregulated genes. Our strategy was validated on the human ANT4 gene which encodes the fourth isoform of the mitochondrial adenine nucleotide translocator specifically expressed during spermatogenesis. The movement of sperm flagella is driven mainly by ATP generated by glycolytic pathways, and the specific induction of the mitochondrial ANT4 protein presented an interesting puzzle. We analysed the sequences of the promoters, introns and exons of 30 mammalian ANT4 genes and constructed regulatory models. The whole human genome and promoter database were screened for genes that were potentially regulated by the generated models. 80% of the identified co-regulated genes encoded proteins with specific roles in spermatogenesis and with functions linked to male reproduction. Our in silico study enabled us to precise the specific role of the ANT4 isoform in spermatozoid bioenergetics.
authors.affiliation: INRA, UMR 1019, UNH, F-63122 St Genès-Champanelle, France.
authors.forename: Pierre-Yves
authors.initials: PY
authors.lastname: Dupont
authors.forename: Georges
authors.initials: G
authors.lastname: Stepien
mesh_terms: D000818:Animals; D001483:Base Sequence; D019295:Computational Biology / Q000379:methods*; D005786:Gene Expression Regulation; D015894:Genome, Human / Q000235:genetics; D006019:Glycolysis; D006801:Humans; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D000226:Mitochondrial ADP, ATP Translocases / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010802:Phylogeny; D011401:Promoter Regions, Genetic / Q000235:genetics; D013094:Spermatozoa / Q000378:metabolism*; D024363:Transcription Initiation Site
chemical_list: C518774:SLC25A31 protein, human; D000226:Mitochondrial ADP, ATP Translocases