Variations in the epigenetic regulation of lineage-specific genes among human pluripotent stem cell lines

► hESCs have canonical epigenetic regulation in pluripotency marker genes unlike hiPSC. ► Transcriptional and epigenetic levels of oncogenes and developmental genes differ among hPSCs. ► Partially-reprogrammed hiPSCs shows abnormal histone modifications. Pluripotent stem cells (PSCs) have unique tra...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2012-07, Vol.424 (2), p.331-337
Main Authors: Kim, Hyemin, Kim, Dongkyu, Jang, Mi-Jin, Han, Yong-Mahn
Format: Article
Language:English
Subjects:
Antigens, Surface - metabolism
Cell Lineage - genetics
Epigenesis, Genetic
Fibroblasts - cytology
Gene expression
Genetic Markers
Genetic Variation
Histone modification
Histones - metabolism
Human embryonic stem cells
Humans
Induced pluripotent stem cells
Induced Pluripotent Stem Cells - metabolism
Induced Pluripotent Stem Cells - physiology
Octamer Transcription Factor-3 - metabolism
Proteoglycans - metabolism
Stage-Specific Embryonic Antigens - metabolism
Transcription, Genetic
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Summary:► hESCs have canonical epigenetic regulation in pluripotency marker genes unlike hiPSC. ► Transcriptional and epigenetic levels of oncogenes and developmental genes differ among hPSCs. ► Partially-reprogrammed hiPSCs shows abnormal histone modifications. Pluripotent stem cells (PSCs) have unique transcriptional regulatory networks and epigenetic states that are involved in maintaining pluripotency. In this study, the transcriptional levels and histone modifications of lineage-specific genes were compared for human ESC (hESC) lines and human induced pluripotent stem cell (hiPSC) lines. Expression of the pluripotency marker genes, OCT4, SOX2, and NANOG, was largely modulated in hESCs by permissive histone marks, whereas hiPSC lines showed differential histone modifications in the gene promoters. The permissive histone mark, H3K4me3, predominantly contributed to expression of the oncogene, c-MYC, in hESC lines, whereas histone modifications of the c-MYC promoter varied between hiPSC lines. Interestingly, the transcriptional levels and epigenetic marks in the promoters of the developmental genes such as SOX17, T, and NESTIN varied among individual hiPSC lines. In particular, a partially-reprogrammed hiPSC cell line showed lower frequencies of permissive and repressive histone marks in the promoters of most genes, indicating incomplete epigenetic reprogramming. Our data indicate that respective hPSCs have distinct epigenetic signatures of lineage-specific genes, thereby leading to in their propensities to follow a particular differentiation pathway.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2012.06.122