Theoretical analysis of Polycomb-Trithorax systems predicts that poised chromatin is bistable and not bivalent
| Autor: | Sneppen, Kim, Ringrose, Leonie |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Bistability Chromosomal Proteins Non-Histone Science Population Polycomb-Group Proteins General Physics and Astronomy 02 engineering and technology Trithorax-group proteins Models Biological Article General Biochemistry Genetics and Molecular Biology Epigenesis Genetic Histones 03 medical and health sciences Histone post-translational modifications Drosophila Proteins Nucleosome Epigenetics lcsh:Science education Epigenesis education.field_of_study Multidisciplinary Chemistry fungi Histone-Lysine N-Methyltransferase General Chemistry 021001 nanoscience & nanotechnology Chromatin Gene regulation Nucleosomes Enzymes Cell biology Histone Code 030104 developmental biology Computer modelling lcsh:Q Systems biology 0210 nano-technology Myeloid-Lymphoid Leukemia Protein Bivalent chromatin |
| Zdroj: | Nature Communications, Vol 10, Iss 1, Pp 1-18 (2019) Nature Communications Sneppen, K & Ringrose, L 2019, ' Theoretical analysis of Polycomb-Trithorax systems predicts that poised chromatin is bistable and not bivalent ', Nature Communications, vol. 10, 2133 . https://doi.org/10.1038/s41467-019-10130-2 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-019-10130-2 |
| Popis: | Polycomb (PcG) and Trithorax (TrxG) group proteins give stable epigenetic memory of silent and active gene expression states, but also allow poised states in pluripotent cells. Here we systematically address the relationship between poised, active and silent chromatin, by integrating 73 publications on PcG/TrxG biochemistry into a mathematical model comprising 144 nucleosome modification states and 8 enzymatic reactions. Our model predicts that poised chromatin is bistable and not bivalent. Bivalent chromatin, containing opposing active and silent modifications, is present as an unstable background population in all system states, and different subtypes co-occur with active and silent chromatin. In contrast, bistability, in which the system switches frequently between stable active and silent states, occurs under a wide range of conditions at the transition between monostable active and silent system states. By proposing that bistability and not bivalency is associated with poised chromatin, this work has implications for understanding the molecular nature of pluripotency. Polycomb and Trithorax group proteins regulate silent and active gene expression states, but also allow poised states in pluripotent cells. Here the authors present a mathematical model that integrates data on Polycomb/ Trithorax biochemistry into a single coherent framework which predicts that poised chromatin is not bivalent as previously proposed, but is bistable, meaning that the system switches frequently between stable active and silent states. |
| Databáze: | OpenAIRE |
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