Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler.
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
02 2022
02 2022
Historique:
received:
24
02
2021
accepted:
14
12
2021
pubmed:
9
2
2022
medline:
20
4
2022
entrez:
8
2
2022
Statut:
ppublish
Résumé
How multiple epigenetic layers and transcription factors (TFs) interact to facilitate brain development is largely unknown. Here, to systematically map the regulatory landscape of neural differentiation in the mouse neocortex, we profiled gene expression and chromatin accessibility in single cells and integrated these data with measurements of enhancer activity, DNA methylation and three-dimensional genome architecture in purified cell populations. This allowed us to identify thousands of new enhancers, their predicted target genes and the temporal relationships between enhancer activation, epigenome remodeling and gene expression. We characterize specific neuronal transcription factors associated with extensive and frequently coordinated changes across multiple epigenetic modalities. In addition, we functionally demonstrate a new role for Neurog2 in directly mediating enhancer activity, DNA demethylation, increasing chromatin accessibility and facilitating chromatin looping in vivo. Our work provides a global view of the gene regulatory logic of lineage specification in the cerebral cortex.
Identifiants
pubmed: 35132236
doi: 10.1038/s41593-021-01002-4
pii: 10.1038/s41593-021-01002-4
pmc: PMC8825286
doi:
Substances chimiques
Basic Helix-Loop-Helix Transcription Factors
0
Chromatin
0
Nerve Tissue Proteins
0
Neurog2 protein, mouse
0
Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
154-167Informations de copyright
© 2022. The Author(s).
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