Dynamic genetic regulation of gene expression during cellular differentiation

Dynamic genetic regulation of gene expression during cellular differentiation

Genetic regulation of gene expression is dynamic, as transcription can change during cell differentiation and across cell types. We mapped expression quantitative trait loci (eQTLs) throughout differentiation to elucidate the dynamics of genetic effects on cell type-specific gene expression. We gene...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) Vol. 364; no. 6447; pp. 1287 - 1290
Main Authors: Strober, B J, Elorbany, R, Rhodes, K, Krishnan, N, Tayeb, K, Battle, A, Gilad, Y
Format: Journal Article
Language:English
Published: United States The American Association for the Advancement of Science 28-06-2019
Subjects:
Biotechnology
Body Composition
Body mass
Body mass index
Body size
Cardiomyocytes
Cell differentiation
Cell Differentiation - genetics
Cell Line
Cell lines
Developmental Stages
Differentiation (biology)
Enhancers
Gene expression
Gene Expression Regulation
Gene mapping
Gene regulation
Gene sequencing
Genetic diversity
Genetic effects
Genetic variance
Genetics
Humans
Individualized Instruction
Myocytes, Cardiac - cytology
Nonlinear dynamics
Phenotypes
Pluripotency
Pluripotent Stem Cells - cytology
Quantitative Trait Loci
Ribonucleic acid
RNA
Sequence Analysis, RNA
Stem cells
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Summary:Genetic regulation of gene expression is dynamic, as transcription can change during cell differentiation and across cell types. We mapped expression quantitative trait loci (eQTLs) throughout differentiation to elucidate the dynamics of genetic effects on cell type-specific gene expression. We generated time-series RNA sequencing data, capturing 16 time points during the differentiation of induced pluripotent stem cells to cardiomyocytes, in 19 human cell lines. We identified hundreds of dynamic eQTLs that change over time, with enrichment in enhancers of relevant cell types. We also found nonlinear dynamic eQTLs, which affect only intermediate stages of differentiation and cannot be found by using data from mature tissues. These fleeting genetic associations with gene regulation may explain some of the components of complex traits and disease. We highlight one example of a nonlinear eQTL that is associated with body mass index.
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These authors contributed equally to this work.
Author contributions: YG and AB conceived the study. RE and KR performed the experiments. KT developed split-GPM. BS analyzed the data, with assistance from NK. All authors wrote the paper. YG and AB supervised this project.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.aaw0040