Diverse epigenetic profile of novel human embryonic stem cell lines.
Human embryonic stem cells (hESCs) are a promising model for studying mechanisms of regulation of early development and differentiation. OCT4, NANOG, OCT4-related genes and some others were recently described to be important in pluripotency maintenance. Lesser is known about molecular mechanisms involved in their regulation. Apart from genetic regulation of gene expression epigenetic events, particularly methylation, play an important role in early development. Using RT-PCR we studied the expression of pluripotency-related genes OCT4, NANOG, DPPA3 and DPPA5 during hESCs differentiation to embryoid bodies. Analysis of methylation profiles of promoter or putative regulatory regions of the indicated genes demonstrated that expression of the pluripotency-maintaining genes correlated with their methylation status, whereas methylation of DPPA3 and DPPA5 varied between cell lines. We propose that DNA methylation underlies the developmental stage-specific mechanisms of pluripotency-related genes expression and reactivation and may have an impact on differentiation potential of hESC lines.
Lagarkova
Maria A
MA
Institute of Gene Biology, Russian Academy of Sciences, Moscow, Russia.
Volchkov
Pavel Y
PY
Lyakisheva
Anna V
AV
Philonenko
Elena S
ES
Kiselev
Sergei L
SL
D024506:5' Flanking Region / Q000235:genetics; D002460:Cell Line; D002868:Chromosomal Proteins, Non-Histone; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D004622:Embryo, Mammalian / Q000166:cytology*; D044127:Epigenesis, Genetic / Q000235:genetics*; D005091:Exons / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3 / Q000235:genetics; D039904:Pluripotent Stem Cells / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D011506:Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism*
D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C466105:DPPA3 protein, human; C507363:Dppa5 protein, human; D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; D011506:Proteins; D012333:RNA, Messenger