Heterochromatin dynamics during the differentiation process revealed by the DNA methylation reporter mouse, methylRO

Jun Ueda, Kazumitsu Maehara, Daisuke Mashiko, Takako Ichinose, Tatsuma Yao, Mayuko Hori, Yuko Sato, Hiroshi Kimura, Yasuyuki Ohkawa, Kazuo Yamagata

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

In mammals, DNA is methylated at CpG sites, which play pivotal roles in gene silencing and chromatin organization. Furthermore, DNA methylation undergoes dynamic changes during development, differentiation, and in pathological processes. The conventional methods represent snapshots; therefore, the dynamics of this marker within living organisms remains unclear. To track this dynamics, we made a knockin mouse that expresses a red fluorescent protein (RFP)-fused methyl-CpG-binding domain (MBD) protein from the ROSA26 locus ubiquitously; we named it MethylRO (methylation probe in ROSA26 locus). Using this mouse, we performed RFP-mediated methylated DNA immunoprecipitation sequencing (MeDIP-seq), whole-body section analysis, and live-cell imaging. We discovered that mobility and pattern of heterochromatin as well as DNA methylation signal intensity inside the nuclei can be markers for cellular differentiation status. Thus, the MethylRO mouse represents a powerful bioresource and technique for DNA methylation dynamics studies in developmental biology, stem cell biology, as well as in disease states.

Original languageEnglish
Pages (from-to)910-924
Number of pages15
JournalStem Cell Reports
Volume2
Issue number6
DOIs
Publication statusPublished - Jun 3 2014

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All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Genetics
  • Developmental Biology
  • Cell Biology

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