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

First Author  Willemin A Year  2021
Journal  PLoS Genet Volume  17
Issue  7 Pages  e1009691
PubMed ID  34292939 Mgi Jnum  J:308529
Mgi Id  MGI:6729861 Doi  10.1371/journal.pgen.1009691
Citation  Willemin A, et al. (2021) Induction of a chromatin boundary in vivo upon insertion of a TAD border. PLoS Genet 17(7):e1009691
abstractText  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.
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