Cargando…
cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression
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 t...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817524/ https://www.ncbi.nlm.nih.gov/pubmed/31495490 http://dx.doi.org/10.1016/j.ajhg.2019.08.003 |
_version_ | 1783463440780623872 |
---|---|
author | Watts, Jason A. Burdick, Joshua Daigneault, Jillian Zhu, Zhengwei Grunseich, Christopher Bruzel, Alan Cheung, Vivian G. |
author_facet | Watts, Jason A. Burdick, Joshua Daigneault, Jillian Zhu, Zhengwei Grunseich, Christopher Bruzel, Alan Cheung, Vivian G. |
author_sort | Watts, Jason A. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6817524 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-68175242020-04-03 cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression Watts, Jason A. Burdick, Joshua Daigneault, Jillian Zhu, Zhengwei Grunseich, Christopher Bruzel, Alan Cheung, Vivian G. Am J Hum Genet Article 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. Elsevier 2019-10-03 2019-09-05 /pmc/articles/PMC6817524/ /pubmed/31495490 http://dx.doi.org/10.1016/j.ajhg.2019.08.003 Text en © 2019 The Author(s) http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Article Watts, Jason A. Burdick, Joshua Daigneault, Jillian Zhu, Zhengwei Grunseich, Christopher Bruzel, Alan Cheung, Vivian G. cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression |
title | cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression |
title_full | cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression |
title_fullStr | cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression |
title_full_unstemmed | cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression |
title_short | cis Elements that Mediate RNA Polymerase II Pausing Regulate Human Gene Expression |
title_sort | cis elements that mediate rna polymerase ii pausing regulate human gene expression |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6817524/ https://www.ncbi.nlm.nih.gov/pubmed/31495490 http://dx.doi.org/10.1016/j.ajhg.2019.08.003 |
work_keys_str_mv | AT wattsjasona ciselementsthatmediaternapolymeraseiipausingregulatehumangeneexpression AT burdickjoshua ciselementsthatmediaternapolymeraseiipausingregulatehumangeneexpression AT daigneaultjillian ciselementsthatmediaternapolymeraseiipausingregulatehumangeneexpression AT zhuzhengwei ciselementsthatmediaternapolymeraseiipausingregulatehumangeneexpression AT grunseichchristopher ciselementsthatmediaternapolymeraseiipausingregulatehumangeneexpression AT bruzelalan ciselementsthatmediaternapolymeraseiipausingregulatehumangeneexpression AT cheungviviang ciselementsthatmediaternapolymeraseiipausingregulatehumangeneexpression |