Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Dynamic Transcriptome, DNA Methylome, and DNA Hydroxymethylome Networks During T-Cell Lineage Commitment

  • Yoon, Byoung-Ha (Department of Functional Genomics, University of Science and Technology (UST)) ;
  • Kim, Mirang (Department of Functional Genomics, University of Science and Technology (UST)) ;
  • Kim, Min-Hyeok (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Kim, Hee-Jin (Genome Editing Research Center, Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Jeong-Hwan (Genome Editing Research Center, Personalized Genomic Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kim, Jong Hwan (Department of Functional Genomics, University of Science and Technology (UST)) ;
  • Kim, Jina (Department of Functional Genomics, University of Science and Technology (UST)) ;
  • Kim, Yong Sung (Department of Functional Genomics, University of Science and Technology (UST)) ;
  • Lee, Daeyoup (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Kang, Suk-Jo (Department of Biological Sciences, Korea Advanced Institute of Science and Technology) ;
  • Kim, Seon-Young (Department of Functional Genomics, University of Science and Technology (UST))
  • Received : 2018.05.21
  • Accepted : 2018.10.18
  • Published : 2018.11.30
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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.

Keywords

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