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Contribution of genetic variation and developmental stage to methylome dynamics in myeloid differentiation

Xiang Chen, Yiping Fan, Jinjun Cheng, Beisi Xu, Yong-Dong Wang, Donald Yergeau, John Easton, James R. Downing, Jinghui Zhang
doi: https://doi.org/10.1101/132985
Xiang Chen
1Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
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  • For correspondence: xiang.chen@stjude.org jinghui.zhang@stjude.org
Yiping Fan
1Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
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Jinjun Cheng
2Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
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Beisi Xu
1Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
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Yong-Dong Wang
1Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
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Donald Yergeau
1Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
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John Easton
1Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
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James R. Downing
2Department of Pathology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
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Jinghui Zhang
1Department of Computational Biology, St. Jude Children’s Research Hospital, Memphis, Tennessee, USA
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  • For correspondence: xiang.chen@stjude.org jinghui.zhang@stjude.org
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Abstract

DNA methylation is important to establish a cell’s developmental identity. It also modulates cellular responses to endogenous developmental stimuli or environmental changes. We designed an in vitro myeloid differentiation model to analyze the genetic and developmental contribution to methylome dynamics using whole-genome bisulfide sequencing and transcriptome sequencing. Using a recursive partitioning approach, we identified 34,502 differentially methylated regions (DMRs) associated with genetic background and/or developmental stimuli. Specifically, 23,792 DMRs (69%) were significantly associated with inter-individual variations, of which 82% were associated with genetic polymorphisms in cis. Notably, inter-individual variations further modified 57 of 212 (26%) developmental DMRs with transcriptomic responses. Our study presents a novel analytical approach to determine the bona fide genetic contribution embedded in outlier patterns of CpG-SNPs in individual methylomes. This approach can be used to study genetic and epigenetic mechanisms underlying differential responses to developmental stimuli, environmental changes, and inter-individual differences in drug responses.

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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.
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Posted May 01, 2017.
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Contribution of genetic variation and developmental stage to methylome dynamics in myeloid differentiation
Xiang Chen, Yiping Fan, Jinjun Cheng, Beisi Xu, Yong-Dong Wang, Donald Yergeau, John Easton, James R. Downing, Jinghui Zhang
bioRxiv 132985; doi: https://doi.org/10.1101/132985
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Contribution of genetic variation and developmental stage to methylome dynamics in myeloid differentiation
Xiang Chen, Yiping Fan, Jinjun Cheng, Beisi Xu, Yong-Dong Wang, Donald Yergeau, John Easton, James R. Downing, Jinghui Zhang
bioRxiv 132985; doi: https://doi.org/10.1101/132985

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