RESUMO
Transcription of non-protein-coding DNA (ncDNA) and its noncoding RNA (ncRNA) products are beginning to emerge as key regulators of gene expression. We previously identified a regulatory system in Saccharomyces cerevisiae whereby transcription of intergenic ncDNA (SRG1) represses transcription of an adjacent protein-coding gene (SER3) through transcription interference. We now provide evidence that SRG1 transcription causes repression of SER3 by directing a high level of nucleosomes over SRG1, which overlaps the SER3 promoter. Repression by SRG1 transcription is dependent on the Spt6 and Spt16 transcription elongation factors. Significantly, spt6 and spt16 mutations reduce nucleosome levels over the SER3 promoter without reducing intergenic SRG1 transcription, strongly suggesting that nucleosome levels, not transcription levels, cause SER3 repression. Finally, we show that spt6 and spt16 mutations allow transcription factor access to the SER3 promoter. Our results raise the possibility that transcription of ncDNA may contribute to nucleosome positioning on a genome-wide scale where, in some cases, it negatively impacts protein-DNA interactions.
Assuntos
DNA Intergênico/metabolismo , Regulação Fúngica da Expressão Gênica , Nucleossomos/metabolismo , Saccharomyces cerevisiae/metabolismo , Transcrição Gênica , DNA Intergênico/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Grupo de Alta Mobilidade/metabolismo , Chaperonas de Histonas , Mutação/genética , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Fosfoglicerato Desidrogenase/metabolismo , Regiões Promotoras Genéticas , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Temperatura , Fatores de Elongação da Transcrição/genética , Fatores de Elongação da Transcrição/metabolismoRESUMO
BACKGROUND: The purpose of this study was to assess the effects of dental flossing on the microbial composition of interproximal plaque samples in matched twins. METHODS: The study was a two-treatment, examiner-masked, randomized, parallel-group, controlled study. Fifty-one twin pairs between 12 and 21 years of age were randomized to a 2-week supervised and unsupervised treatment regimen consisting of tongue brushing and toothbrushing or tongue brushing and toothbrushing plus flossing. The reverse-capture checkerboard hybridization assay was used to assess levels (abundance) of 26 microbial species in interproximal plaque samples collected from six sites per subject. An integrative computational predictive model estimated average changes in microbial abundance patterns of selected bacterial species from baseline to 2 weeks by comparing treatment groups. RESULTS: After the 2-week study period, putative periodontal pathogens and cariogenic bacteria were overabundant in the group that did not floss compared to the group that performed flossing. Those included Treponema denticola, Porphyromonas gingivalis, Tannerella forsythia (previously T. forsythensis), Prevotella intermedia, Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans), and Streptococcus mutans. Microbial species that are not consistent with the development of periodontal disease or dental caries were overabundant in the group that did floss compared to the non-flossing group. CONCLUSION: In a well-matched twin cohort, tooth and tongue brushing plus flossing significantly decreased the abundance of microbial species associated with periodontal disease and dental caries after a 2-week program.
