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Title 

Dynamic transcriptome, DNA methylome, and DNA hydroxymethylome networks during T-cell lineage commitment

Authors 

Byeong Ha YounMirang KimM H KimHee Jin KimJeong Hwan KimJong-Hwan KimJina KimYong Sung KimD LeeS J KangSeon-Young Kim

Publisher 

Springer Verlag (Germany)

Issue Date 

2018

Citation 

Molecules and Cells

Keywords 

DNA hydroxymethylationDNA methylationT-cell development

Abstract 

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.

ISSN 

1016-8478

Link 

http://dx.doi.org/10.14348/molcells.2018.0213

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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