Dynamic changes in DNA methylation and hydroxymethylation when hES cells undergo differentiation toward a neuronal lineage

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Title
Dynamic changes in DNA methylation and hydroxymethylation when hES cells undergo differentiation toward a neuronal lineage
Author(s)
Mi Rang Kim; Y K Park; T W Kang; S H Lee; Y H Rhee; Jong Lyul Park; D Lee; D Lee; Seon-Young Kim; Yong Sung Kim
Bibliographic Citation
Human Molecular Genetics, vol. 23, no. 3, pp. 657-667
Publication Year
2014
Abstract
DNA methylation and hydroxymethylation have been implicated in normal development and differentiation, but our knowledge is limited about the genome-wide distribution of 5-methylcytosine (5 mC) and 5-hydroxymethylcytosine (5 hmC) during cellular differentiation. Using an in vitro model system of gradual differentiation of human embryonic stem (hES) cells into ventral midbrain-type neural precursor cells and terminally into dopamine neurons,weobserved dramatic genome-wide changes in 5 mCand 5 hmCpatterns duringlineagecommitment. The 5 hmCpattern was dynamic in promoters, exons and enhancers. DNA hydroxymethylation within the gene body was associated with gene activation. The neurogenesis-related genes NOTCH1, RGMA and AKT1 acquired 5 hmCin the gene body and were up-regulated during differentiation.DNAmethylation in the promoter was associated with gene repression. The pluripotency-related genes POU5F1, ZFP42 and HMGA1 acquired 5 mC in their promoters and were down-regulated during differentiation. Promoter methylation also acted as a locking mechanism to maintain gene silencing. The mesoderm development-related genes NKX2-8, TNFSF11 and NFATC1 acquired promoter methylation during neural differentiation even though they were already silenced inhEScells.Ourfindings will help elucidate the molecularmechanisms underlying lineage-specific differentiation of pluripotent stem cells during human embryonic development.
ISSN
0964-6906
Publisher
Oxford Univ Press
DOI
http://dx.doi.org/10.1093/hmg/ddt453
Type
Article
Appears in Collections:
Aging Convergence Research Center > 1. Journal Articles
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