Modeling Single-Molecule Conformations of the HoxD Region in Mouse Embryonic Stem and Cortical Neuronal Cells
| Autor: | Mario Nicodemi, Andrea Esposito, Andrea M. Chiariello, Carlo Annunziatella, Mattia Conte, Raffaele Campanile, Luca Fiorillo, Guillaume Andrey, Antonella Prisco, Simona Bianco |
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| Přispěvatelé: | Bianco, S., Annunziatella, C., Andrey, G., Chiariello, A. M., Esposito, A., Fiorillo, L., Prisco, A., Conte, Mattia, Campanile, Raffaele, Nicodemi, M. |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Cell type statistical physic Molecular Conformation Locus (genetics) General Biochemistry Genetics and Molecular Biology polymer physic 03 medical and health sciences Mice 0302 clinical medicine PHASE-SEPARATION SPATIAL-ORGANIZATION CHROMATIN-STRUCTURE GENOME ARCHITECTURE DOMAINS DYNAMICS GENES chromatin architecture Gene duplication computer simulation Animals ddc:576.5 Epigenetics Gene Embryonic Stem Cells Neurons biology differentiation Embryonic stem cell single cell Cell biology 030104 developmental biology Histone Cardiovascular and Metabolic Diseases CTCF biology.protein hoxd 030217 neurology & neurosurgery |
| Zdroj: | Cell Reports, Vol. 28, No 6 (2019) pp. 1574-1583.e4 Cell reports 28 (2019): 1574–1583. doi:10.1016/j.celrep.2019.07.013 info:cnr-pdr/source/autori:Bianco S.; Annunziatella C.; Andrey G.; Chiariello A.M.; Esposito A.; Fiorillo L.; Prisco A.; Conte M.; Campanile R.; Nicodemi M./titolo:Modeling Single-Molecule Conformations of the HoxD Region in Mouse Embryonic Stem and Cortical Neuronal Cells/doi:10.1016%2Fj.celrep.2019.07.013/rivista:Cell reports/anno:2019/pagina_da:1574/pagina_a:1583/intervallo_pagine:1574–1583/volume:28 |
| ISSN: | 2211-1247 |
| DOI: | 10.1016/j.celrep.2019.07.013 |
| Popis: | Complex architectural rearrangements are associated to the control of the HoxD genes in different cell types; yet, how they are implemented in single cells remains unknown. By use of polymer models, we dissect the locus 3D structure at the single DNA molecule level in mouse embryonic stem and cortical neuronal cells, as the HoxD cluster changes from a poised to a silent state. Our model describes published Hi-C, 3-way 4C, and FISH data with high accuracy and is validated against independent 4C data on the Nsi-SB 0.5-Mb duplication and on triple contacts. It reveals the mode of action of compartmentalization on the regulation of the HoxD genes that have gene- and cell-type-specific multi-way interactions with their regulatory elements and high cell-to-cell variability. It shows that TADs and higher-order 3D structures, such as metaTADs, associate with distinct combinations of epigenetic factors, including but not limited to CCCTC-binding factor (CTCF) and histone marks. Bianco et al. reconstruct the 3D structure of the murine HoxD locus by using polymer models at the single DNA molecule level. The locus architecture rearranges upon differentiation from embryonic stem cells to cortical neurons in connection to epigenetic changes, as cell-type- and gene-specific multi-way contacts are established with regulatory elements. |
| Databáze: | OpenAIRE |
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