Skip to main content

Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation.

Publication ,  Journal Article
Keele, GR; Quach, BC; Israel, JW; Chappell, GA; Lewis, L; Safi, A; Simon, JM; Cotney, P; Crawford, GE; Valdar, W; Rusyn, I; Furey, TS
Published in: PLoS Genet
January 2020

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

January 2020

Volume

16

Issue

1

Start / End Page

e1008537

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Phosphatidylinositol 3-Kinases
  • Organ Specificity
  • Mice
  • Male
  • Lung
  • Liver
  • Kruppel-Like Transcription Factors
  • Kidney
  • Developmental Biology
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Keele, G. R., Quach, B. C., Israel, J. W., Chappell, G. A., Lewis, L., Safi, A., … Furey, T. S. (2020). Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation. PLoS Genet, 16(1), e1008537. https://doi.org/10.1371/journal.pgen.1008537
Keele, Gregory R., Bryan C. Quach, Jennifer W. Israel, Grace A. Chappell, Lauren Lewis, Alexias Safi, Jeremy M. Simon, et al. “Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation.PLoS Genet 16, no. 1 (January 2020): e1008537. https://doi.org/10.1371/journal.pgen.1008537.
Keele GR, Quach BC, Israel JW, Chappell GA, Lewis L, Safi A, et al. Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation. PLoS Genet. 2020 Jan;16(1):e1008537.
Keele, Gregory R., et al. “Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation.PLoS Genet, vol. 16, no. 1, Jan. 2020, p. e1008537. Pubmed, doi:10.1371/journal.pgen.1008537.
Keele GR, Quach BC, Israel JW, Chappell GA, Lewis L, Safi A, Simon JM, Cotney P, Crawford GE, Valdar W, Rusyn I, Furey TS. Integrative QTL analysis of gene expression and chromatin accessibility identifies multi-tissue patterns of genetic regulation. PLoS Genet. 2020 Jan;16(1):e1008537.

Published In

PLoS Genet

DOI

EISSN

1553-7404

Publication Date

January 2020

Volume

16

Issue

1

Start / End Page

e1008537

Location

United States

Related Subject Headings

  • Quantitative Trait Loci
  • Phosphatidylinositol 3-Kinases
  • Organ Specificity
  • Mice
  • Male
  • Lung
  • Liver
  • Kruppel-Like Transcription Factors
  • Kidney
  • Developmental Biology