Epigenetic signatures and temporal expression of lineage-specific genes in hESCs during differentiation to hepatocytes in vitro.
Embryonic stem cells (ESCs) maintain unique epigenetic states to maintain their pluripotency. Differentiation of ESCs into specialized cell types requires changes in these epigenetic states. However, the dynamics of epigenetic marks found in hESCs during differentiation are poorly understood. Here, we report the variation in the dynamics of epigenetic modifications associated with the expression of lineage-specific genes during differentiation of hESCs to hepatocytes in vitro. The promoter regions of pluripotency marker genes characterized by permissive histone marks such as trimethylation of H3 at lysine 4 (H3K4me3) and acetylation of H3 at lysine 9 (H3K9ac) in hESCs were instead enriched with repressive histone marks such as dimethylation of H3 at lysine 9 (H3K9me2), trimethylation of H3 at lysine 9 (H3K9me3) and trimethylation of H3 at lysine 27 (H3K27me3) during differentiation to hepatocytes. Interestingly, expression of definitive endoderm marker genes containing bivalent and non-bivalent domains may be modulated by a marked reduction in H3K27me3 and a significant enhancement of permissive marks such as H3K4me3 and H3K9ac during hESC differentiation. Expression of hepatocyte marker genes regulated by histone modifications was similar to that of pluripotency marker genes. Our findings provide insight into the epigenetic mechanisms regulating expression of developmental genes. Of particular interest, they may be differentially regulated either in a bivalent or non-bivalent domain manner during hESC differentiation.
Department of Biological Sciences and Center for Stem Cell Differentiation, KAIST, Daejeon 305-701, Republic of Korea.
Hyemin
H
Kim
Mi-Jin
MJ
Jang
Man-Jong
MJ
Kang
Yong-Mahn
YM
Han
D002454:Cell Differentiation; D019070:Cell Lineage / Q000235:genetics*; D002478:Cells, Cultured; D002874:Chromosome Mapping; D019175:DNA Methylation; D053595:Embryonic Stem Cells / Q000166:cytology* / Q000378:metabolism*; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D005819:Genetic Markers; D022781:Hepatocytes / Q000166:cytology* / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D006801:Humans; D008239:Lysine / Q000378:metabolism; D011401:Promoter Regions, Genetic; D054730:Protein Interaction Domains and Motifs; D020133:Reverse Transcriptase Polymerase Chain Reaction
D005819:Genetic Markers; D006657:Histones; D008239:Lysine