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Multimodal profiling of the transcriptional regulatory landscape of the developing mouse cortex identifies Neurog2 as a key epigenome remodeler.

Nat. Neurosci. 25, 154-167 (2022)
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Open Access Gold (Paid Option)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Gene-regulation; Chromatin; Dna; Differentiation; Accessibility; Organization; Mechanisms; Mutations; Programs; Domains
ISSN (print) / ISBN 1097-6256
e-ISSN 1546-1726
Quellenangaben Volume: 25, Issue: 2, Pages: 154-167 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)
Helmholtz Artifical Intelligence Cooperation Unit (HAICU)
Grants Deutsche Forschungsgemeinschaft (German Research Foundation)