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

Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression

Celine L St. Pierre, Juan F Macias-Velasco, Jessica P Wayhart, Li Yin, Clay F Semenkovich, View ORCID ProfileHeather A Lawson
doi: https://doi.org/10.1101/2021.09.09.459642
Celine L St. Pierre
1Department of Genetics, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Juan F Macias-Velasco
1Department of Genetics, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jessica P Wayhart
1Department of Genetics, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Li Yin
2Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Clay F Semenkovich
2Department of Medicine, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Heather A Lawson
1Department of Genetics, Washington University School of Medicine, 660 South Euclid Ave, Saint Louis, MO, USA
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Heather A Lawson
  • For correspondence: lawson@wustl.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

ABSTRACT

Allele-specific expression (ASE) is a phenomenon where one allele is preferentially expressed over the other. Genetic and epigenetic factors cause ASE by altering the final allelic composition of a gene’s product, leading to expression imbalances that can have functional consequences on phenotypes. Environmental signals also impact allele-specific gene regulation, but how they contribute to this crosstalk remains understudied. Here, we explored how allelic genotype, parent-of-origin, tissue type, sex, and dietary fat simultaneously influence ASE biases in a F1 reciprocal cross mouse model. Male and female mice from a F1 reciprocal cross of the LG/J and SM/J strains were fed a high-fat or low-fat diet. We harnessed strain-specific variants to distinguish between two classes of ASE: parent-of-origin dependent (unequal expression based on an allele’s parental origin) and sequence dependent (unequal expression based on an allele’s nucleotide identity). We present a comprehensive genome-wide map of ASE patterns across three metabolically-relevant tissues and nine environmental contexts. We find that both ASE classes are highly dependent on tissue type and environmental context. They vary across metabolic tissues, between males and females, and in response to dietary fat levels. Surprisingly, we also find several genes with inconsistent ASE biases that switched direction across tissues and/or contexts (e.g. SM/J biased in one cohort, LG/J biased in another). Together, our results provide novel insights into how genetic, epigenetic, and environmental mechanisms govern allele-specific gene regulation, which is an essential step towards deciphering the genotype to phenotype map.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • CL St. Pierre: stpierrec{at}wustl.edu, JF Macias-Velasco: juanfmacias{at}wustl.edu, JP Wayhart: jwayhart{at}genetics.wustl.edu, L Yin: liyin{at}wustl.edu, CF Semenkovich: csemenko{at}wustl.edu, HA Lawson: hlawson{at}genetics.wustl.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-NC-ND 4.0 International license.
Back to top
PreviousNext
Posted September 10, 2021.
Download PDF

Supplementary Material

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.
Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression
(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
Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression
Celine L St. Pierre, Juan F Macias-Velasco, Jessica P Wayhart, Li Yin, Clay F Semenkovich, Heather A Lawson
bioRxiv 2021.09.09.459642; doi: https://doi.org/10.1101/2021.09.09.459642
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
Genetic, epigenetic, and environmental mechanisms govern allele-specific gene expression
Celine L St. Pierre, Juan F Macias-Velasco, Jessica P Wayhart, Li Yin, Clay F Semenkovich, Heather A Lawson
bioRxiv 2021.09.09.459642; doi: https://doi.org/10.1101/2021.09.09.459642

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 (4672)
  • Biochemistry (10337)
  • Bioengineering (7655)
  • Bioinformatics (26286)
  • Biophysics (13497)
  • Cancer Biology (10666)
  • Cell Biology (15412)
  • Clinical Trials (138)
  • Developmental Biology (8487)
  • Ecology (12803)
  • Epidemiology (2067)
  • Evolutionary Biology (16822)
  • Genetics (11381)
  • Genomics (15462)
  • Immunology (10596)
  • Microbiology (25165)
  • Molecular Biology (10198)
  • Neuroscience (54382)
  • Paleontology (399)
  • Pathology (1665)
  • Pharmacology and Toxicology (2889)
  • Physiology (4333)
  • Plant Biology (9234)
  • Scientific Communication and Education (1585)
  • Synthetic Biology (2554)
  • Systems Biology (6770)
  • Zoology (1461)