Department of Molecular, Cell and Cancer Biology
Bioinformatics | Biophysics | Developmental Biology | Genetics and Genomics | Molecular Biology | Structural Biology
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.
Gene regulation, Nuclear organization
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DOI of Published Version
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
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.