Dynamics as a cause for the nanoscale organization of the genome
| Autor: | Haitham A. Shaban, Roman Barth, Genevieve Fourel |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular lcsh:QH426-470 Computational biology Granger-causality Biology Genome Genome organization 03 medical and health sciences Deep Learning Tumor Cells Cultured medicine Humans Nucleosome lcsh:QH573-671 Chromatin dynamics 030304 developmental biology Genomic organization Physics Stochastic Processes 0303 health sciences Active polymers Deep-PALM lcsh:Cytology Dynamics (mechanics) 030302 biochemistry & molecular biology 4D genome Cell Biology Chromatin Assembly and Disassembly Chromatin Nanostructures lcsh:Genetics medicine.anatomical_structure Biological system Nucleus Research Article Research Paper |
| Zdroj: | Nucleus, 11(1) Nucleus article-version (VoR) Version of Record Nucleus, Vol 11, Iss 1, Pp 83-98 (2020) |
| ISSN: | 1949-1034 |
| DOI: | 10.1080/19491034.2020.1763093 |
| Popis: | Chromatin ‘blobs’ were recently identified by live super-resolution imaging as pervasive, but transient and dynamic structural entities consisting of a few associating nucleosomes. The origin and functional implications of these blobs are, however, unknown. Following these findings, we explore whether causal relationships exist between parameters characterizing the chromatin blob dynamics and structure, by adapting a framework for spatio-temporal Granger-causality inference. Our analysis reveals that chromatin dynamics is a key determinant of both blob area and local density. However, such causality can only be demonstrated in small areas (10 – 20%) of the nucleus, highlighting that chromatin dynamics and structure at the nanoscale is dominated by stochasticity. Pixels for which the inter-blob distance can be effectively demonstrated to depend on chromatin dynamics appears as clump in the nucleus, and display both a higher blob density and higher local dynamics as compared with the rest of the nucleus. Furthermore, we show that the theory of active semiflexible polymers can be invoked to provide potential mechanisms leading to the organization of chromatin into blobs. Based on active motion-inducing effectors, this framework qualitatively recapitulates experimental observations and predicts that chromatin blobs might be formed stochastically by a collapse of local polymer segments consisting of a few nucleosomes. Our results represent a first step towards elucidating the mechanisms that govern the dynamic and stochastic organization of chromatin in a cell nucleus. |
| Databáze: | OpenAIRE |
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