Simulating topological domains in human chromosomes with a fitting-free model
We discuss a polymer model for the 3D organization of human chromosomes. A chromosome is represented by a string of beads, with each bead being "colored" according to 1D bioinformatic data (e.g., chromatin state, histone modification, GC content). Individual spheres (representing bi- and m...
| Main Authors: | , , , , , , |
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| 格式: | Journal article |
| 語言: | English |
| 出版: |
Taylor and Francis
2016
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| _version_ | 1826258047924699136 |
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| author | Brackley, C Michieletto, D Mouvet, F Johnson, J Kelly, S Cook, P Marenduzzo, D |
| author_facet | Brackley, C Michieletto, D Mouvet, F Johnson, J Kelly, S Cook, P Marenduzzo, D |
| author_sort | Brackley, C |
| collection | OXFORD |
| description | We discuss a polymer model for the 3D organization of human chromosomes. A chromosome is represented by a string of beads, with each bead being "colored" according to 1D bioinformatic data (e.g., chromatin state, histone modification, GC content). Individual spheres (representing bi- and multi-valent transcription factors) can bind reversibly and selectively to beads with the appropriate color. During molecular dynamics simulations, the factors bind, and the string spontaneously folds into loops, rosettes, and topologically-associating domains (TADs). This organization occurs in the absence of any specified interactions between distant DNA segments, or between transcription factors. A comparison with Hi-C data shows that simulations predict the location of most boundaries between TADs correctly. The model is "fitting-free" in the sense that it does not use Hi-C data as an input; consequently, one of its strengths is that it can - in principle - be used to predict the 3D organization of any region of interest, or whole chromosome, in a given organism, or cell line, in the absence of existing Hi-C data. We discuss how this simple model might be refined to include more transcription factors and binding sites, and to correctly predict contacts between convergent CTCF binding sites. |
| first_indexed | 2024-03-06T18:27:51Z |
| format | Journal article |
| id | oxford-uuid:08993eae-901f-4cf8-bccf-be4cf1b39a0c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T18:27:51Z |
| publishDate | 2016 |
| publisher | Taylor and Francis |
| record_format | dspace |
| spelling | oxford-uuid:08993eae-901f-4cf8-bccf-be4cf1b39a0c2022-03-26T09:13:42ZSimulating topological domains in human chromosomes with a fitting-free modelJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:08993eae-901f-4cf8-bccf-be4cf1b39a0cEnglishSymplectic Elements at OxfordTaylor and Francis2016Brackley, CMichieletto, DMouvet, FJohnson, JKelly, SCook, PMarenduzzo, DWe discuss a polymer model for the 3D organization of human chromosomes. A chromosome is represented by a string of beads, with each bead being "colored" according to 1D bioinformatic data (e.g., chromatin state, histone modification, GC content). Individual spheres (representing bi- and multi-valent transcription factors) can bind reversibly and selectively to beads with the appropriate color. During molecular dynamics simulations, the factors bind, and the string spontaneously folds into loops, rosettes, and topologically-associating domains (TADs). This organization occurs in the absence of any specified interactions between distant DNA segments, or between transcription factors. A comparison with Hi-C data shows that simulations predict the location of most boundaries between TADs correctly. The model is "fitting-free" in the sense that it does not use Hi-C data as an input; consequently, one of its strengths is that it can - in principle - be used to predict the 3D organization of any region of interest, or whole chromosome, in a given organism, or cell line, in the absence of existing Hi-C data. We discuss how this simple model might be refined to include more transcription factors and binding sites, and to correctly predict contacts between convergent CTCF binding sites. |
| spellingShingle | Brackley, C Michieletto, D Mouvet, F Johnson, J Kelly, S Cook, P Marenduzzo, D Simulating topological domains in human chromosomes with a fitting-free model |
| title | Simulating topological domains in human chromosomes with a fitting-free model |
| title_full | Simulating topological domains in human chromosomes with a fitting-free model |
| title_fullStr | Simulating topological domains in human chromosomes with a fitting-free model |
| title_full_unstemmed | Simulating topological domains in human chromosomes with a fitting-free model |
| title_short | Simulating topological domains in human chromosomes with a fitting-free model |
| title_sort | simulating topological domains in human chromosomes with a fitting free model |
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