Characterization of DNA methylation change in stem cell marker genes during differentiation of human embryonic stem cells.
Pluripotent human embryonic stem cells (hESCs) have the distinguishing feature of innate capacity to allow indefinite self-renewal. This attribute continues until specific constraints or restrictions, such as DNA methylation, are imposed on the genome, usually accompanied by differentiation. With the aim of utilizing DNA methylation as a sign of early differentiation, we probed the genomic regions of hESCs, particularly focusing on stem cell marker (SCM) genes to identify regulatory sequences that display differentiation-sensitive alterations in DNA methylation. We show that the promoter regions of OCT4 and NANOG, but not SOX2, REX1 and FOXD3, undergo significant methylation during hESCs differentiation in which SCM genes are substantially repressed. Thus, following exposure to differentiation stimuli, OCT4 and NANOG gene loci are modified relatively rapidly by DNA methylation. Accordingly, we propose that the DNA methylation states of OCT4 and NANOG sequences may be utilized as barometers to determine the extent of hESC differentiation.
Yeo
Seungeun
S
Center for Regenerative Medicine, KRIBB, Eoeun-Dong, Yuseong-Gu, Daejeon 305-333, Republic of Korea.
Jeong
Sangkyun
S
Kim
Janghwan
J
Han
Jee-Soo
JS
Han
Yong-Mahn
YM
Kang
Yong-Kook
YK
D002454:Cell Differentiation / Q000187:drug effects; D003469:Culture; D004247:DNA / Q000378:metabolism*; D019175:DNA Methylation / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000235:genetics; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation; D005819:Genetic Markers; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D014212:Tretinoin / Q000494:pharmacology
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D014212:Tretinoin; D004247:DNA