CTCF-mediated topological boundaries during development foster appropriate gene regulation
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyProgram in Systems Biology
Document Type
Journal ArticlePublication Date
2016-12-15Keywords
CTCFHox gene regulation
Polycomb/Trithorax
TADs
chromatin and epigenetics
chromosomal conformation
Biochemistry
Computational Biology
Developmental Biology
Genomics
Molecular Biology
Structural Biology
Systems Biology
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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.Source
Genes Dev. 2016 Dec 15;30(24):2657-2662. doi: 10.1101/gad.288324.116. Link to article on publisher's site.DOI
10.1101/gad.288324.116Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49973PubMed ID
28087711Related Resources
Link to Article in PubMedRights
© 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/.Distribution License
http://creativecommons.org/licenses/by-nc/4.0/ae974a485f413a2113503eed53cd6c53
10.1101/gad.288324.116
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Except where otherwise noted, this item's license is described as © 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/.
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