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About:
Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation
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covidontheweb.inria.fr
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Type:
Academic Article
research paper
schema:ScholarlyArticle
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type
Academic Article
research paper
schema:ScholarlyArticle
isDefinedBy
Covid-on-the-Web dataset
has title
Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation
Creator
Safi, Alexias
Lewis, Lauren
Chappellid, Grace
Cotneyid, Paul
Crawford, Gregory
Fureyid, Terrence
Id, Jennifer
Keele Id, Gregory
Quach Id, Bryan
Rusynid, Ivan
Simonid, Jeremy
Valdarid, William
Source
PMC
abstract
Gene transcription profiles across tissues are largely defined by the activity of regulatory elements, most of which correspond to regions of accessible chromatin. Regulatory element activity is in turn modulated by genetic variation, resulting in variable transcription rates across individuals. The interplay of these factors, however, is poorly understood. Here we characterize expression and chromatin state dynamics across three tissues—liver, lung, and kidney—in 47 strains of the Collaborative Cross (CC) mouse population, examining the regulation of these dynamics by expression quantitative trait loci (eQTL) and chromatin QTL (cQTL). QTL whose allelic effects were consistent across tissues were detected for 1,101 genes and 133 chromatin regions. Also detected were eQTL and cQTL whose allelic effects differed across tissues, including local-eQTL for Pik3c2g detected in all three tissues but with distinct allelic effects. Leveraging overlapping measurements of gene expression and chromatin accessibility on the same mice from multiple tissues, we used mediation analysis to identify chromatin and gene expression intermediates of eQTL effects. Based on QTL and mediation analyses over multiple tissues, we propose a causal model for the distal genetic regulation of Akr1e1, a gene involved in glycogen metabolism, through the zinc finger transcription factor Zfp985 and chromatin intermediates. This analysis demonstrates the complexity of transcriptional and chromatin dynamics and their regulation over multiple tissues, as well as the value of the CC and related genetic resource populations for identifying specific regulatory mechanisms within cells and tissues.
has issue date
2020-01-21
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xsd:dateTime
)
bibo:doi
10.1371/journal.pgen.1008537
bibo:pmid
31961859
has license
cc-by
sha1sum (hex)
1029b20dd40ca982d05b80adad4c125beb10217b
schema:url
https://doi.org/10.1371/journal.pgen.1008537
resource representing a document's title
Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation
has PubMed Central identifier
PMC7010298
has PubMed identifier
31961859
schema:publication
PLoS Genet
resource representing a document's body
covid:1029b20dd40ca982d05b80adad4c125beb10217b#body_text
is
schema:about
of
named entity 'genes'
named entity 'multiple'
named entity 'glycogen'
named entity 'chromatin'
named entity 'expression'
named entity 'MULTI'
named entity 'TISSUES'
named entity 'MODULATED'
covid:arg/1029b20dd40ca982d05b80adad4c125beb10217b
named entity 'CHROMATIN ACCESSIBILITY'
named entity 'DEFINED'
named entity 'CONSISTENT'
named entity 'BUT'
named entity 'DETECTED'
named entity 'POPULATION'
named entity 'CELLS'
named entity 'HERE'
named entity 'ANALYSIS'
named entity 'TURN'
named entity 'LARGELY'
named entity 'MECHANISMS'
named entity 'INDIVIDUALS'
named entity 'GENETIC REGULATION'
named entity 'GENETIC VARIATION'
named entity 'GENETIC REGULATION'
named entity 'ACROSS'
named entity 'TO IDENTIFY'
named entity 'MICE'
named entity 'REGIONS'
named entity 'CHROMATIN ACCESSIBILITY'
named entity 'TISSUE'
named entity 'GENE EXPRESSION'
named entity 'A GENE'
named entity 'RELATED'
named entity 'LIVER'
named entity 'COMPLEXITY'
named entity 'GENE TRANSCRIPTION'
named entity 'GENES'
named entity '2C101'
named entity 'ACTIVITY'
named entity 'GENE EXPRESSION'
named entity 'MULTIPLE'
named entity 'POORLY'
named entity 'ZINC FINGER TRANSCRIPTION FACTOR'
named entity 'STRAINS'
named entity 'IDENTIFYING'
named entity 'MOUSE'
named entity 'OVERLAPPING'
named entity 'TRANSCRIPTION'
named entity 'THESE'
named entity 'CROSS'
named entity 'EXPRESSION'
named entity 'LUNG'
named entity 'LOCAL'
named entity 'THEIR'
named entity '133'
named entity 'DISTINCT'
named entity 'AKR1E1'
named entity 'REGULATORY'
named entity 'REGULATORY ELEMENT'
named entity 'USED'
named entity 'GENETIC RESOURCE'
named entity 'REGULATION'
named entity 'SPECIFIC'
named entity 'INTERMEDIATES'
named entity 'QTL'
named entity 'ACCESSIBLE'
named entity 'PIK3C2G'
named entity 'DISTAL'
named entity 'RESULTING IN'
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