The epigenetic bivalency of core pancreatic β-cell transcription factor genes within mouse pluripotent embryonic stem cells is not affected by knockdown of the polycomb repressive complex 2, SUZ12.
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 β-cells relative to expression in an embryonic stem cell line. Epigenetic analysis of the Oct4, Utf1, Nanog and...
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| Autores principales: | , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2014
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/e0b7d16cffca41579bc916049a8f393e |
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| Sumario: | 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 β-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 β-cells) transcription factor genes in embryonic stem cells and a β-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 β-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 β-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 β-cell transcription factors in embryonic stem cells and was reduced MIN6. Knock-down of SUZ12 in embryonic stem cells, however, did not reduce the level of histone 3 trimethylated at lysine 27 at β-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 β-cell transcription factors in embryonic stem cells. |
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