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摘要
This study assesses changes in activator and repressor modifications to histones associated with the core transcription factor genes most highly upregulated or downregulated in pancreatic beta-cells relative to expression in an embryonic stem cell line. Epigenetic analysis of the Oct4, Utf1, Nanog and Sox2 (pluripotency) and Pdx1, Nkx6.1, Nkx2.2 and MafA (pancreatic beta-cells) transcription factor genes in embryonic stem cells and a beta-cell line (MIN6) showed the pluripotency genes were enriched for active (histone 3 trimethylated at lysine 4 and histone 3 acetylated at lysine 9) and depleted of repressor modifications (histone 3 trimethylated at lysine 27 and histone 3 trimethylated at lysine 9) around the transcription start site in mouse embryonic stem cells (D3), and this was reversed in MIN6 cells. The beta-cell transcription factors were bivalently enriched for activating (histone 3 trimethylated at lysine 4) and repressor (histone 3 trimethylated at lysine 27) modifications in embryonic stem cells but were monovalent for the activator modification (histone 3 trimethylated at lysine 4) in the beta-cells. The polycomb repressor complex 2 acts as a histone 3 lysine 27 methylase and an essential component of this complex, SUZ12, was enriched at the beta-cell transcription factors in embryonic stem cells and was reduced MIN6. Knockdown of SUZ12 in embryonic stem cells, however, did not reduce the level of histone 3 trimethylated at lysine 27 at beta-cell transcription factor loci or break the transcriptional repression of these genes in embryonic stem cells. This study shows the reduction in the total SUZ12 level was not a sufficient cause of the resolution of the epigenetic bivalency of b-cell transcription factors in embryonic stem cells.
- 出版日期2014-5-20
- 单位河北医科大学
