Alteration of genome folding via contact domain boundary insertion.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
10 2020
10 2020
Historique:
received:
25
08
2019
accepted:
23
07
2020
pubmed:
2
9
2020
medline:
25
11
2020
entrez:
2
9
2020
Statut:
ppublish
Résumé
Animal chromosomes are partitioned into contact domains. Pathogenic domain disruptions can result from chromosomal rearrangements or perturbation of architectural factors. However, such broad-scale alterations are insufficient to define the minimal requirements for domain formation. Moreover, to what extent domains can be engineered is just beginning to be explored. In an attempt to create contact domains, we inserted a 2-kb DNA sequence underlying a tissue-invariant domain boundary-containing a CTCF-binding site (CBS) and a transcription start site (TSS)-into 16 ectopic loci across 11 chromosomes, and characterized its architectural impact. Depending on local constraints, this fragment variably formed new domains, partitioned existing ones, altered compartmentalization and initiated contacts reflecting chromatin loop extrusion. Deletions of the CBS or the TSS individually or in combination within inserts revealed its distinct contributions to genome folding. Altogether, short DNA insertions can suffice to shape the spatial genome in a manner influenced by chromatin context.
Identifiants
pubmed: 32868908
doi: 10.1038/s41588-020-0680-8
pii: 10.1038/s41588-020-0680-8
pmc: PMC7541666
mid: NIHMS1614764
doi:
Substances chimiques
CCCTC-Binding Factor
0
CTCF protein, human
0
Chromatin
0
DNA-Binding Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1076-1087Subventions
Organisme : NIMH NIH HHS
ID : R01 MH120269
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK054937
Pays : United States
Organisme : NIDDK NIH HHS
ID : R24 DK106766
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK127405
Pays : United States
Organisme : NHLBI NIH HHS
ID : U01 HL129998
Pays : United States
Commentaires et corrections
Type : CommentIn
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