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

Abstract

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. (C) 2012 Elsevier Inc. All rights reserved.