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Quantitative modelling predicts the impact of DNA methylation on RNA polymerase II traffic.


ABSTRACT: Patterns of gene expression are primarily determined by proteins that locally enhance or repress transcription. While many transcription factors target a restricted number of genes, others appear to modulate transcription levels globally. An example is MeCP2, an abundant methylated-DNA binding protein that is mutated in the neurological disorder Rett syndrome. Despite much research, the molecular mechanism by which MeCP2 regulates gene expression is not fully resolved. Here, we integrate quantitative, multidimensional experimental analysis and mathematical modeling to indicate that MeCP2 is a global transcriptional regulator whose binding to DNA creates "slow sites" in gene bodies. We hypothesize that waves of slowed-down RNA polymerase II formed behind these sites travel backward and indi

SUBMITTER: Cholewa-Waclaw J 

PROVIDER: S-EPMC6660794 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature