Mapping the Global Chromatin Connectivity Network for Sox2 Function in Neural Stem Cell Maintenance.
ChIA-PET
SOX2
chromatin connectivity
neural stem cells
transcription factors
Journal
Cell stem cell
ISSN: 1875-9777
Titre abrégé: Cell Stem Cell
Pays: United States
ID NLM: 101311472
Informations de publication
Date de publication:
07 03 2019
07 03 2019
Historique:
received:
30
01
2018
revised:
16
07
2018
accepted:
06
02
2019
entrez:
9
3
2019
pubmed:
9
3
2019
medline:
24
4
2020
Statut:
ppublish
Résumé
The SOX2 transcription factor is critical for neural stem cell (NSC) maintenance and brain development. Through chromatin immunoprecipitation (ChIP) and chromatin interaction analysis (ChIA-PET), we determined genome-wide SOX2-bound regions and Pol II-mediated long-range chromatin interactions in brain-derived NSCs. SOX2-bound DNA was highly enriched in distal chromatin regions interacting with promoters and carrying epigenetic enhancer marks. Sox2 deletion caused widespread reduction of Pol II-mediated long-range interactions and decreased gene expression. Genes showing reduced expression in Sox2-deleted cells were significantly enriched in interactions between promoters and SOX2-bound distal enhancers. Expression of one such gene, Suppressor of Cytokine Signaling 3 (Socs3), rescued the self-renewal defect of Sox2-ablated NSCs. Our work identifies SOX2 as a major regulator of gene expression through connections to the enhancer network in NSCs. Through the definition of such a connectivity network, our study shows the way to the identification of genes and enhancers involved in NSC maintenance and neurodevelopmental disorders.
Identifiants
pubmed: 30849367
pii: S1934-5909(19)30046-3
doi: 10.1016/j.stem.2019.02.004
pmc: PMC6506828
pii:
doi:
Substances chimiques
Chromatin
0
SOXB1 Transcription Factors
0
Sox2 protein, mouse
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
462-476.e6Subventions
Organisme : NHGRI NIH HHS
ID : UM1 HG009409
Pays : United States
Organisme : Medical Research Council
ID : FC0010089
Pays : United Kingdom
Organisme : NCI NIH HHS
ID : P30 CA034196
Pays : United States
Organisme : NIDDK NIH HHS
ID : U54 DK107967
Pays : United States
Organisme : Wellcome Trust
ID : FC0010089
Pays : United Kingdom
Organisme : Cancer Research UK
ID : FC0010089
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/K005316/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
Copyright © 2019 Elsevier Inc. All rights reserved.
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