In silico structural modelling of multiple epigenetic marks on DNA
Summary: There are four known epigenetic cytosine modifications in mammals: 5mC, 5hmC, 5fC and 5caC. The biological effects of 5mC are well understood but the roles of the remaining modifications remain elusive. Experimental and computational studies suggest that a single epigenetic mark has little...
| Main Authors: | , , , , |
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| Format: | Journal article |
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Oxford University Press
2017
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| _version_ | 1797067575373332480 |
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| author | Krawczyk, K Demharter, S Knapp, B Deane, C Minary, P |
| author_facet | Krawczyk, K Demharter, S Knapp, B Deane, C Minary, P |
| author_sort | Krawczyk, K |
| collection | OXFORD |
| description | Summary: There are four known epigenetic cytosine modifications in mammals: 5mC, 5hmC, 5fC and 5caC. The biological effects of 5mC are well understood but the roles of the remaining modifications remain elusive. Experimental and computational studies suggest that a single epigenetic mark has little structural effect but six of them can radically change the structure of DNA to a new form, FDNA. Investigating the collective effect of multiple epigenetic marks requires the ability to interrogate all possible combinations of epigenetic states (e.g. methylated/non-methylated) along a stretch of DNA. Experiments on such complex systems are only feasible on small, isolated examples and there currently exist no systematic computational solutions to this problem. We address this issue by extending the use of Natural Move Monte Carlo to simulate the conformations of epigenetic marks. We validate our protocol by reproducing in silico experimental observations from two recently published high-resolution crystal structures that contain epigenetic marks 5hmC and 5fC. We further demonstrate that our protocol correctly finds either the F-DNA or the B-DNA states more energetically favorable depending on the configuration of the epigenetic marks. We hope that the computational efficiency and ease of use of this novel simulation framework would form the basis for future protocols and facilitate our ability to rapidly interrogate diverse epigenetic systems. Availability: The code together with examples and tutorials are available from http://www.cs.ox.ac.uk/mosaics |
| first_indexed | 2024-03-06T21:58:17Z |
| format | Journal article |
| id | oxford-uuid:4db5c593-cf8e-483c-a436-1f39d437d1c0 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T21:58:17Z |
| publishDate | 2017 |
| publisher | Oxford University Press |
| record_format | dspace |
| spelling | oxford-uuid:4db5c593-cf8e-483c-a436-1f39d437d1c02022-03-26T15:56:56ZIn silico structural modelling of multiple epigenetic marks on DNAJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:4db5c593-cf8e-483c-a436-1f39d437d1c0Symplectic Elements at OxfordOxford University Press2017Krawczyk, KDemharter, SKnapp, BDeane, CMinary, PSummary: There are four known epigenetic cytosine modifications in mammals: 5mC, 5hmC, 5fC and 5caC. The biological effects of 5mC are well understood but the roles of the remaining modifications remain elusive. Experimental and computational studies suggest that a single epigenetic mark has little structural effect but six of them can radically change the structure of DNA to a new form, FDNA. Investigating the collective effect of multiple epigenetic marks requires the ability to interrogate all possible combinations of epigenetic states (e.g. methylated/non-methylated) along a stretch of DNA. Experiments on such complex systems are only feasible on small, isolated examples and there currently exist no systematic computational solutions to this problem. We address this issue by extending the use of Natural Move Monte Carlo to simulate the conformations of epigenetic marks. We validate our protocol by reproducing in silico experimental observations from two recently published high-resolution crystal structures that contain epigenetic marks 5hmC and 5fC. We further demonstrate that our protocol correctly finds either the F-DNA or the B-DNA states more energetically favorable depending on the configuration of the epigenetic marks. We hope that the computational efficiency and ease of use of this novel simulation framework would form the basis for future protocols and facilitate our ability to rapidly interrogate diverse epigenetic systems. Availability: The code together with examples and tutorials are available from http://www.cs.ox.ac.uk/mosaics |
| spellingShingle | Krawczyk, K Demharter, S Knapp, B Deane, C Minary, P In silico structural modelling of multiple epigenetic marks on DNA |
| title | In silico structural modelling of multiple epigenetic marks on DNA |
| title_full | In silico structural modelling of multiple epigenetic marks on DNA |
| title_fullStr | In silico structural modelling of multiple epigenetic marks on DNA |
| title_full_unstemmed | In silico structural modelling of multiple epigenetic marks on DNA |
| title_short | In silico structural modelling of multiple epigenetic marks on DNA |
| title_sort | in silico structural modelling of multiple epigenetic marks on dna |
| work_keys_str_mv | AT krawczykk insilicostructuralmodellingofmultipleepigeneticmarksondna AT demharters insilicostructuralmodellingofmultipleepigeneticmarksondna AT knappb insilicostructuralmodellingofmultipleepigeneticmarksondna AT deanec insilicostructuralmodellingofmultipleepigeneticmarksondna AT minaryp insilicostructuralmodellingofmultipleepigeneticmarksondna |