Dynamic Transcriptome, DNA Methylome, and DNA Hydroxymethylome Networks During T-Cell Lineage Commitment

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The stepwise development of T cells from a multipotent precursor is guided by diverse mechanisms, including interactions among lineage-specific transcription factors (TFs) and epigenetic changes, such as DNA methylation and hydroxymethylation, which play crucial roles in mammalian development and lineage commitment. To elucidate the transcriptional networks and epigenetic mechanisms underlying T-cell lineage commitment, we investigated genome-wide changes in gene expression, DNA methylation and hydroxymethylation among populations representing five successive stages of T-cell development (DN3, DN4, DP, CD4+, and CD8+) by performing RNA-seq, MBD-seq and hMeDIP-seq, respectively. The most significant changes in the transcriptomes and epigenomes occurred during the DN4 to DP transition. During the DP stage, many genes involved in chromatin modification were up-regulated and exhibited dramatic changes in DNA hydroxymethylation. We also observed 436 alternative splicing events, and approximately 57% (252) of these events occurred during the DP stage. Many stage-specific, differentially methylated regions were observed near the stage-specific, differentially expressed genes. The dynamic changes in DNA methylation and hydroxymethylation were associated with the recruitment of stage-specific TFs. We elucidated interactive networks comprising TFs, chromatin modifiers, and DNA methylation and hope that this study provides a framework for the understanding of the molecular networks underlying T-cell lineage commitment.
Publisher
KOREAN SOC MOLECULAR & CELLULAR BIOLOGY
Issue Date
2018-11
Language
English
Article Type
Article
Citation

MOLECULES AND CELLS, v.41, no.11, pp.953 - 963

ISSN
1016-8478
DOI
10.14348/molcells.2018.0213
URI
http://hdl.handle.net/10203/248284
Appears in Collection
BS-Journal Papers(저널논문)
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