Assuntos
Inteligência Artificial , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/prevenção & controle , Estilo de Vida Saudável , Tecnologia de Sensoriamento Remoto/instrumentação , Comportamento de Redução do Risco , Telemedicina , Aptidão Cardiorrespiratória , Doenças Cardiovasculares/fisiopatologia , Monitores de Aptidão Física , Nível de Saúde , Humanos , Aplicativos Móveis , Aptidão Física , Valor Preditivo dos Testes , Smartphone , Telemedicina/instrumentaçãoRESUMO
Sequences with the potential to form intramolecular G-quadruplexes (G4-structures) are found in highly nonrandom distributions in the genomes of diverse organisms. These sequences are associated with nucleic acid metabolic processes ranging from transcription and translation to recombination and telomere function. Here we review different computational methods for identifying potential G4-forming sequences and provide protocols for their implementation. We also discuss methods for assessing the significance and specificity of associations between the sequences and different biological functions.
Assuntos
Biologia Computacional/métodos , Quadruplex G , Guanina/química , Primers do DNA/química , HumanosRESUMO
Although well studied in vitro, the in vivo functions of G-quadruplexes (G4-DNA and G4-RNA) are only beginning to be defined. Recent studies have demonstrated enrichment for sequences with intramolecular G-quadruplex forming potential (QFP) in transcriptional promoters of humans, chickens and bacteria. Here we survey the yeast genome for QFP sequences and similarly find strong enrichment for these sequences in upstream promoter regions, as well as weaker but significant enrichment in open reading frames (ORFs). Further, four findings are consistent with roles for QFP sequences in transcriptional regulation. First, QFP is correlated with upstream promoter regions with low histone occupancy. Second, treatment of cells with N-methyl mesoporphyrin IX (NMM), which binds G-quadruplexes selectively in vitro, causes significant upregulation of loci with QFP-possessing promoters or ORFs. NMM also causes downregulation of loci connected with the function of the ribosomal DNA (rDNA), which itself has high QFP. Third, ORFs with QFP are selectively downregulated in sgs1 mutants that lack the G4-DNA-unwinding helicase Sgs1p. Fourth, a screen for yeast mutants that enhance or suppress growth inhibition by NMM revealed enrichment for chromatin and transcriptional regulators, as well as telomere maintenance factors. These findings raise the possibility that QFP sequences form bona fide G-quadruplexes in vivo and thus regulate transcription.
