UMMS Affiliation
Department of Molecular, Cell and Cancer Biology
Publication Date
2020-06-01
Document Type
Article
Disciplines
Bioinformatics | Biophysics | Developmental Biology | Genetics and Genomics | Molecular Biology | Structural Biology
Abstract
Mammalian gene expression patterns are controlled by regulatory elements, which interact within topologically associating domains (TADs). The relationship between activation of regulatory elements, formation of structural chromatin interactions and gene expression during development is unclear. Here, we present Tiled-C, a low-input chromosome conformation capture (3C) technique. We use this approach to study chromatin architecture at high spatial and temporal resolution through in vivo mouse erythroid differentiation. Integrated analysis of chromatin accessibility and single-cell expression data shows that regulatory elements gradually become accessible within pre-existing TADs during early differentiation. This is followed by structural re-organization within the TAD and formation of specific contacts between enhancers and promoters. Our high-resolution data show that these enhancer-promoter interactions are not established prior to gene expression, but formed gradually during differentiation, concomitant with progressive upregulation of gene activity. Together, these results provide new insight into the close, interdependent relationship between chromatin architecture and gene regulation during development.
Keywords
Gene regulation, Nuclear organization
Rights and Permissions
Copyright © The Author(s) 2020. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
DOI of Published Version
10.1038/s41467-020-16598-7
Source
Oudelaar AM, Beagrie RA, Gosden M, de Ornellas S, Georgiades E, Kerry J, Hidalgo D, Carrelha J, Shivalingam A, El-Sagheer AH, Telenius JM, Brown T, Buckle VJ, Socolovsky M, Higgs DR, Hughes JR. Dynamics of the 4D genome during in vivo lineage specification and differentiation. Nat Commun. 2020 Jun 1;11(1):2722. doi: 10.1038/s41467-020-16598-7. PMID: 32483172; PMCID: PMC7264236. Link to article on publisher's site
Journal/Book/Conference Title
Nature communications
Related Resources
PubMed ID
32483172
Repository Citation
Oudelaar AM, Hidalgo D, Socolovsky M, Higgs DR, Hughes JR. (2020). Dynamics of the 4D genome during in vivo lineage specification and differentiation. Open Access Articles. https://doi.org/10.1038/s41467-020-16598-7. Retrieved from https://escholarship.umassmed.edu/oapubs/4275
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Included in
Bioinformatics Commons, Biophysics Commons, Developmental Biology Commons, Genetics and Genomics Commons, Molecular Biology Commons, Structural Biology Commons
Comments
Full author list omitted for brevity. For the full list of authors, see article.