Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Biochemistry | Computational Biology | Developmental Biology | Genomics | Molecular Biology | Structural Biology | Systems Biology
The genome is organized into repeating topologically associated domains (TADs), each of which is spatially isolated from its neighbor by poorly understood boundary elements thought to be conserved across cell types. Here, we show that deletion of CTCF (CCCTC-binding factor)-binding sites at TAD and sub-TAD topological boundaries that form within the HoxA and HoxC clusters during differentiation not only disturbs local chromatin domain organization and regulatory interactions but also results in homeotic transformations typical of Hox gene misregulation. Moreover, our data suggest that CTCF-dependent boundary function can be modulated by competing forces, such as the self-assembly of polycomb domains within the nucleus. Therefore, CTCF boundaries are not merely static structural components of the genome but instead are locally dynamic regulatory structures that control gene expression during development.
CTCF, Hox gene regulation, Polycomb/Trithorax, TADs, chromatin and epigenetics, chromosomal conformation
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© 2016 Narendra et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
DOI of Published Version
Genes Dev. 2016 Dec 15;30(24):2657-2662. doi: 10.1101/gad.288324.116. Link to article on publisher's site.
Genes and development
Narendra, Varun; Bulajic, Milica; Dekker, Job; Mazzoni, Esteban O.; and Reinberg, Danny, "CTCF-mediated topological boundaries during development foster appropriate gene regulation" (2016). Program in Systems Biology Publications and Presentations. 95.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial 4.0 License