Modeling Single-Molecule Conformations of the HoxD Region in Mouse Embryonic Stem and Cortical Neuronal Cells.
chromatin architecture
differentiation
hoxd
polymer physics
single cell
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
06 08 2019
06 08 2019
Historique:
received:
27
07
2018
revised:
24
05
2019
accepted:
02
07
2019
entrez:
8
8
2019
pubmed:
8
8
2019
medline:
10
9
2020
Statut:
ppublish
Résumé
Complex architectural rearrangements are associated to the control of the HoxD genes in different cell types; yet, how they are implemented in single cells remains unknown. By use of polymer models, we dissect the locus 3D structure at the single DNA molecule level in mouse embryonic stem and cortical neuronal cells, as the HoxD cluster changes from a poised to a silent state. Our model describes published Hi-C, 3-way 4C, and FISH data with high accuracy and is validated against independent 4C data on the Nsi-SB 0.5-Mb duplication and on triple contacts. It reveals the mode of action of compartmentalization on the regulation of the HoxD genes that have gene- and cell-type-specific multi-way interactions with their regulatory elements and high cell-to-cell variability. It shows that TADs and higher-order 3D structures, such as metaTADs, associate with distinct combinations of epigenetic factors, including but not limited to CCCTC-binding factor (CTCF) and histone marks.
Identifiants
pubmed: 31390570
pii: S2211-1247(19)30903-9
doi: 10.1016/j.celrep.2019.07.013
pii:
doi:
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
1574-1583.e4Subventions
Organisme : NIDDK NIH HHS
ID : U54 DK107977
Pays : United States
Informations de copyright
Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.