DNA Methylation Directs Polycomb-Dependent 3D Genome Re-organization in Naive Pluripotency
| Autor: | Sari Pennings, Robert S. Illingworth, Heidi K. Mjoseng, John P. Thomson, Iain Williamson, Wendy A. Bickmore, Ilya M. Flyamer, Katy A. Mclaughlin, Richard R. Meehan, Graeme R. Grimes, Ruchi Shukla, Ian R. Adams |
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| Jazyk: | angličtina |
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Male macromolecular substances Biology Genome General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Epigenome Mice 0302 clinical medicine Hi-C Animals ground state Mouse Embryonic Stem Cells/cytology fluorescence in situ hybridization lcsh:QH301-705.5 Genomic organization Regulation of gene expression Mice Knockout DNA methylation Chromatin/genetics reprogramming Mouse Embryonic Stem Cells DNA Methylation Chromatin Assembly and Disassembly pluripotency Chromatin 3D genome Cell biology 030104 developmental biology lcsh:Biology (General) embryonic structures Reprogramming polycomb 030217 neurology & neurosurgery DNA hypomethylation |
| Zdroj: | Cell Reports, Vol 29, Iss 7, Pp 1974-1985.e6 (2019) Cell Reports Mclaughlin, K, Flyamer, I M, Thomson, J P, Mjoseng, H K, Shukla, R, Williamson, I, Grimes, G R, Illingworth, R S, Adams, I R, Pennings, S, Meehan, R R & Bickmore, W A 2019, ' DNA Methylation Directs Polycomb-Dependent 3D Genome Re-organization in Naive Pluripotency ', vol. 29, no. 7, pp. 1974-1985.e6 . https://doi.org/10.1016/j.celrep.2019.10.031 McLaughlin, K, Flyamer, I M, Thomson, J P, Mjoseng, H K, Shukla, R, Williamson, I, Grimes, G R, Illingworth, R S, Adams, I R, Pennings, S, Meehan, R R & Bickmore, W A 2019, ' DNA Methylation Directs Polycomb-Dependent 3D Genome Re-organization in Naive Pluripotency ', Cell Reports, vol. 29, no. 7, pp. 1974-1985.e6 . https://doi.org/10.1016/j.celrep.2019.10.031, https://doi.org/10.1016/j.celrep.2019.10.031 |
| ISSN: | 2211-1247 |
| Popis: | Summary The DNA hypomethylation that occurs when embryonic stem cells (ESCs) are directed to the ground state of naive pluripotency by culturing in two small molecule inhibitors (2i) results in redistribution of polycomb (H3K27me3) away from its target loci. Here, we demonstrate that 3D genome organization is also altered in 2i, with chromatin decompaction at polycomb target loci and a loss of long-range polycomb interactions. By preventing DNA hypomethylation during the transition to the ground state, we are able to restore to ESC in 2i the H3K27me3 distribution, as well as polycomb-mediated 3D genome organization that is characteristic of primed ESCs grown in serum. However, these cells retain the functional characteristics of 2i ground-state ESCs. Our findings demonstrate the central role of DNA methylation in shaping major aspects of 3D genome organization but caution against assuming causal roles for the epigenome and 3D genome in gene regulation and function in ESCs. Graphical Abstract Highlights • The altered 3D genome of 2i ESCs is due to polycomb re-distribution • Stopping DNA hypomethylation and genome re-organization does not affect 2i cell state • Hypomethylated mouse blastocysts have a similar 3D chromatin organization to 2i ESCs McLaughlin et al. demonstrate that the global DNA methylation state directs the PRC-dependent 3D organization of mouse ESCs and probably early blastocysts. Their findings highlight a central role for DNA methylation and its influence on polycomb, in shaping major aspects of 3D genome organization in stem cells. |
| Databáze: | OpenAIRE |
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