Thousands of human and Drosophila genes are regulated at the level of transcript elongation and nucleosomes are likely targets for this regulation. However, the molecular mechanisms of formation of the nucleosomal barrier to transcribing RNA polymerase II (Pol II) and nucleosome survival during/after transcription remain unknown. Here we show that both DNA-histone interactions and Pol II backtracking contribute to formation of the barrier and that nucleosome survival during transcription likely occurs through allosterically stabilized histone-histone interactions. Structural analysis indicates that after Pol II encounters the barrier, the enzyme backtracks and nucleosomal DNA recoils on the octamer, locking Pol II in the arrested state. DNA is displaced from one of the H2A/H2B dimers that remains associated with the octamer. The data reveal the importance of intranucleosomal DNA-protein and protein-protein interactions during conformational changes in the nucleosome structure on transcription. Mechanisms of nucleosomal barrier formation and nucleosome survival during transcription are proposed.
Accumulated data suggests that the gut microbiome can rapidly respond to changes in diet. Consumption of fermented dairy products (FDP) fortified with probiotic microbes may be associated with positive impact on human health. However, the extent and details of the possible impact of FDP consumption on gut community structure tends to vary across individuals. We used microbiome analysis to characterize changes in gut microbiota composition after 30 days of oral intake of a yoghurt fortified with Bifidobacterium animalis subsp. lactis BB-12. 16S rRNA gene sequencing was used to assess the gut microbial composition before and after FDP consumption in healthy adults (n = 150). Paired comparison of gut microbial content demonstrated an increase in presence of potentially beneficial bacteria, particularly, Bifidobacterium genus, as well as Adlercreutzia equolifaciens and Slackia isoflavoniconvertens. At a functional level, an increased capacity to metabolize lactose and synthesize amino acids was observed accompanied by a lowered potential for synthesis of lipopolysaccharides. Cluster analysis revealed that study volunteers segregated into two groups with post-intervention microbiota response that was dependent on the baseline microbial community structure.
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