Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
Contradictory Results

Genome-wide repressive capacity of promoter DNA methylation is revealed through epigenomic manipulation

View ORCID ProfileKeegan Korthauer, View ORCID ProfileRafael A. Irizarry
doi: https://doi.org/10.1101/381145
Keegan Korthauer
1Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, MA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Keegan Korthauer
Rafael A. Irizarry
1Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, MA
2Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Rafael A. Irizarry
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

Abstract

The scientific community is increasingly embracing open science. This growing commitment to open science should be applauded and encouraged, especially when it occurs voluntarily and prior to peer review. Thanks to other researchers’ dedication to open science, we have had the privilege of conducting a reanalysis of a landmark experiment published as a preprint with data made available in a public repository. The study in question found that promoter DNA methylation is frequently insufficient to induce transcriptional repression, which appears to contradict a large body of observational studies showing a strong association between DNA methylation and gene expression. This study was the first to evaluate whether forcibly methylating thousands of DNA promoter regions is sufficient to suppress gene expression. The authors’ data analysis did not find a strong relationship between promoter methylation and transcriptional repression. However, their analyses did not make full use of statistical inference and applied a normalization technique that removes global differences that are representative of the actual biological system. Here we reanalyze the data with an approach that includes statistical inference of differentially methylated regions, as well as a normalization technique that accounts for global expression differences. We find that forced DNA methylation of thousands of promoters overwhelmingly represses gene expression. In addition, we show that complementary epigenetic marks of active transcription are reduced as a result of DNA methylation. Finally, by studying whether these associations are sensitive to the CG density of promoters, we find no substantial differences in the association between promoters with and without a CG island. The code needed to reproduce are analysis is included in the public GitHub repository github.com/kdkorthauer/repressivecapacity.

Footnotes

  • ↵* rafa{at}jimmy.harvard.edu

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted August 01, 2018.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Genome-wide repressive capacity of promoter DNA methylation is revealed through epigenomic manipulation
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Genome-wide repressive capacity of promoter DNA methylation is revealed through epigenomic manipulation
Keegan Korthauer, Rafael A. Irizarry
bioRxiv 381145; doi: https://doi.org/10.1101/381145
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Genome-wide repressive capacity of promoter DNA methylation is revealed through epigenomic manipulation
Keegan Korthauer, Rafael A. Irizarry
bioRxiv 381145; doi: https://doi.org/10.1101/381145

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Genomics
Subject Areas
All Articles
  • Animal Behavior and Cognition (4229)
  • Biochemistry (9108)
  • Bioengineering (6753)
  • Bioinformatics (23944)
  • Biophysics (12102)
  • Cancer Biology (9497)
  • Cell Biology (13742)
  • Clinical Trials (138)
  • Developmental Biology (7616)
  • Ecology (11662)
  • Epidemiology (2066)
  • Evolutionary Biology (15479)
  • Genetics (10620)
  • Genomics (14297)
  • Immunology (9467)
  • Microbiology (22793)
  • Molecular Biology (9078)
  • Neuroscience (48892)
  • Paleontology (355)
  • Pathology (1479)
  • Pharmacology and Toxicology (2565)
  • Physiology (3823)
  • Plant Biology (8309)
  • Scientific Communication and Education (1467)
  • Synthetic Biology (2290)
  • Systems Biology (6172)
  • Zoology (1297)