cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression.

Clicks: 346
ID: 59930
2019
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Abstract
Aberrant gene expression underlies many human diseases. RNA polymerase II (Pol II) pausing is a key regulatory step in transcription. Here, we mapped the locations of RNA Pol II in normal human cells and found that RNA Pol II pauses in a consistent manner across individuals and cell types. At more than 1,000 genes including MYO1E and SESN2, RNA Pol II pauses at precise nucleotide locations. Characterization of these sites shows that RNA Pol II pauses at GC-rich regions that are marked by a sequence motif. Sixty-five percent of the pause sites are cytosines. By differential allelic gene expression analysis, we showed in our samples and a population dataset from the Genotype-Tissue Expression (GTEx) consortium that genes with more paused polymerase have lower expression levels. Furthermore, mutagenesis of the pause sites led to a significant increase in promoter activities. Thus, our data uncover that RNA Pol II pauses precisely at sites with distinct sequence features that in turn regulate gene expression.
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watts2019cisamerican Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Watts, Jason A;Burdick, Joshua;Daigneault, Jillian;Zhu, Zhengwei;Grunseich, Christopher;Bruzel, Alan;Cheung, Vivian G;
Journal American journal of human genetics
Year 2019
DOI
S0002-9297(19)30306-4
URL
Keywords
gene expression transcription rna polymerase rna polymerase pausing

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