Induction of a chromatin boundary in vivo upon insertion of a TAD border.

Mammalian genomes are partitioned into sub-megabase to megabase-sized units of preferential interactions called topologically associating domains or TADs, which are likely important for the proper implementation of gene regulatory processes. These domains provide structural scaffolds for distant cis...

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Autores principales:	Andréa Willemin, Lucille Lopez-Delisle, Christopher Chase Bolt, Marie-Laure Gadolini, Denis Duboule, Eddie Rodriguez-Carballo
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Genetics QH426-470
Acceso en línea:	https://doaj.org/article/258973812dc0457fb34148a8b083a2d4
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spelling	oai:doaj.org-article:258973812dc0457fb34148a8b083a2d42021-12-02T20:02:55ZInduction of a chromatin boundary in vivo upon insertion of a TAD border.1553-73901553-740410.1371/journal.pgen.1009691https://doaj.org/article/258973812dc0457fb34148a8b083a2d42021-07-01T00:00:00Zhttps://doi.org/10.1371/journal.pgen.1009691https://doaj.org/toc/1553-7390https://doaj.org/toc/1553-7404Mammalian genomes are partitioned into sub-megabase to megabase-sized units of preferential interactions called topologically associating domains or TADs, which are likely important for the proper implementation of gene regulatory processes. These domains provide structural scaffolds for distant cis regulatory elements to interact with their target genes within the three-dimensional nuclear space and architectural proteins such as CTCF as well as the cohesin complex participate in the formation of the boundaries between them. However, the importance of the genomic context in providing a given DNA sequence the capacity to act as a boundary element remains to be fully investigated. To address this question, we randomly relocated a topological boundary functionally associated with the mouse HoxD gene cluster and show that it can indeed act similarly outside its initial genomic context. In particular, the relocated DNA segment recruited the required architectural proteins and induced a significant depletion of contacts between genomic regions located across the integration site. The host chromatin landscape was re-organized, with the splitting of the TAD wherein the boundary had integrated. These results provide evidence that topological boundaries can function independently of their site of origin, under physiological conditions during mouse development.Andréa WilleminLucille Lopez-DelisleChristopher Chase BoltMarie-Laure GadoliniDenis DubouleEddie Rodriguez-CarballoPublic Library of Science (PLoS)articleGeneticsQH426-470ENPLoS Genetics, Vol 17, Iss 7, p e1009691 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Genetics QH426-470
spellingShingle	Genetics QH426-470 Andréa Willemin Lucille Lopez-Delisle Christopher Chase Bolt Marie-Laure Gadolini Denis Duboule Eddie Rodriguez-Carballo Induction of a chromatin boundary in vivo upon insertion of a TAD border.
description	Mammalian genomes are partitioned into sub-megabase to megabase-sized units of preferential interactions called topologically associating domains or TADs, which are likely important for the proper implementation of gene regulatory processes. These domains provide structural scaffolds for distant cis regulatory elements to interact with their target genes within the three-dimensional nuclear space and architectural proteins such as CTCF as well as the cohesin complex participate in the formation of the boundaries between them. However, the importance of the genomic context in providing a given DNA sequence the capacity to act as a boundary element remains to be fully investigated. To address this question, we randomly relocated a topological boundary functionally associated with the mouse HoxD gene cluster and show that it can indeed act similarly outside its initial genomic context. In particular, the relocated DNA segment recruited the required architectural proteins and induced a significant depletion of contacts between genomic regions located across the integration site. The host chromatin landscape was re-organized, with the splitting of the TAD wherein the boundary had integrated. These results provide evidence that topological boundaries can function independently of their site of origin, under physiological conditions during mouse development.
format	article
author	Andréa Willemin Lucille Lopez-Delisle Christopher Chase Bolt Marie-Laure Gadolini Denis Duboule Eddie Rodriguez-Carballo
author_facet	Andréa Willemin Lucille Lopez-Delisle Christopher Chase Bolt Marie-Laure Gadolini Denis Duboule Eddie Rodriguez-Carballo
author_sort	Andréa Willemin
title	Induction of a chromatin boundary in vivo upon insertion of a TAD border.
title_short	Induction of a chromatin boundary in vivo upon insertion of a TAD border.
title_full	Induction of a chromatin boundary in vivo upon insertion of a TAD border.
title_fullStr	Induction of a chromatin boundary in vivo upon insertion of a TAD border.
title_full_unstemmed	Induction of a chromatin boundary in vivo upon insertion of a TAD border.
title_sort	induction of a chromatin boundary in vivo upon insertion of a tad border.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/258973812dc0457fb34148a8b083a2d4
work_keys_str_mv	AT andreawillemin inductionofachromatinboundaryinvivouponinsertionofatadborder AT lucillelopezdelisle inductionofachromatinboundaryinvivouponinsertionofatadborder AT christopherchasebolt inductionofachromatinboundaryinvivouponinsertionofatadborder AT marielauregadolini inductionofachromatinboundaryinvivouponinsertionofatadborder AT denisduboule inductionofachromatinboundaryinvivouponinsertionofatadborder AT eddierodriguezcarballo inductionofachromatinboundaryinvivouponinsertionofatadborder
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Induction of a chromatin boundary in vivo upon insertion of a TAD border.

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