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Control of transcriptional pausing by biased thermal fluctuations on repetitive genomic sequences.


ABSTRACT: In the process of transcription elongation, RNA polymerase (RNAP) pauses at highly nonrandom positions across genomic DNA, broadly regulating transcription; however, molecular mechanisms responsible for the recognition of such pausing positions remain poorly understood. Here, using a combination of statistical mechanical modeling and high-throughput sequencing and biochemical data, we evaluate the effect of thermal fluctuations on the regulation of RNAP pausing. We demonstrate that diffusive backtracking of RNAP, which is biased by repetitive DNA sequence elements, causes transcriptional pausing. This effect stems from the increased microscopic heterogeneity of an elongation complex, and thus is entropy-dominated. This report shows a linkage between repetitive sequence elements encoded in the genome and regulation of RNAP pausing driven by thermal fluctuations.

SUBMITTER: Imashimizu M 

PROVIDER: S-EPMC5127303 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Control of transcriptional pausing by biased thermal fluctuations on repetitive genomic sequences.

Imashimizu Masahiko M   Afek Ariel A   Takahashi Hiroki H   Lubkowska Lucyna L   Lukatsky David B DB  

Proceedings of the National Academy of Sciences of the United States of America 20161108 47


In the process of transcription elongation, RNA polymerase (RNAP) pauses at highly nonrandom positions across genomic DNA, broadly regulating transcription; however, molecular mechanisms responsible for the recognition of such pausing positions remain poorly understood. Here, using a combination of statistical mechanical modeling and high-throughput sequencing and biochemical data, we evaluate the effect of thermal fluctuations on the regulation of RNAP pausing. We demonstrate that diffusive bac  ...[more]

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