Journal article
Hybrid Mice Reveal Parent-of-Origin and Cis- and Trans-Regulatory Effects in the Retina
PloS one, Vol.9(10), pp.e109382-e109382
10/23/2014
DOI: 10.1371/journal.pone.0109382
PMCID: PMC4207689
PMID: 25340786
Abstract
A fundamental challenge in genomics is to map DNA sequence variants onto changes in gene expression. Gene expression is regulated by cis-regulatory elements (CREs, i. e., enhancers, promoters, and silencers) and the trans factors (e. g., transcription factors) that act upon them. A powerful approach to dissecting cis and trans effects is to compare F1 hybrids with F0 homozygotes. Using this approach and taking advantage of the high frequency of polymorphisms in wild-derived inbred Cast/EiJ mice relative to the reference strain C57BL/6J, we conducted allele-specific mRNA-seq analysis in the adult mouse retina, a disease-relevant neural tissue. We found that cis effects account for the bulk of gene regulatory divergence in the retina. Many CREs contained functional (i. e., activating or silencing) cis-regulatory variants mapping onto altered expression of genes, including genes associated with retinal disease. By comparing our retinal data with previously published liver data, we found that most of the cis effects identified were tissue-specific. Lastly, by comparing reciprocal F1 hybrids, we identified evidence of imprinting in the retina for the first time. Our study provides a framework and resource for mapping cis-regulatory variants onto changes in gene expression, and underscores the importance of studying cis-regulatory variants in the context of retinal disease.
Details
- Title: Subtitle
- Hybrid Mice Reveal Parent-of-Origin and Cis- and Trans-Regulatory Effects in the Retina
- Creators
- Susan Q. Shen - Washington University in St. LouisErnest Turro - National Health ServiceJoseph C. Corbo - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- PloS one, Vol.9(10), pp.e109382-e109382
- Publisher
- Public Library Science
- DOI
- 10.1371/journal.pone.0109382
- PMID
- 25340786
- PMCID
- PMC4207689
- ISSN
- 1932-6203
- eISSN
- 1932-6203
- Number of pages
- 16
- Grant note
- P30 CA91842 / National Cancer Institute Cancer Center Support Grant; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) Cambridge Biomedical Research Centre 19556 / Cancer Research UK Genome Technology Access Center at Washington University 5T32EY013360-14; R01HG006790; R01EY018826 / National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA National Center for Research Resources (NCRR); United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) C14303/ A10825 / Cancer Research UK UL1RR024992 / Institute of Clinical and Translational Sciences (ICTS)/Clinical & Translational Science Awards (CTSA)
- Language
- English
- Date published
- 10/23/2014
- Academic Unit
- Psychiatry; Iowa Neuroscience Institute
- Record Identifier
- 9984618645502771
Metrics
4 Record Views