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Noack, F. ; Vangelisti, S. ; Ditzer, N.* ; Chong, F. ; Albert, M.* ; Bonev, B.

Joint epigenome profiling reveals cell-type-specific gene regulatory programmes in human cortical organoids.

Nat. Cell Biol. 12, 1873-1883 (2023)
DOI PMC
Open Access Green as soon as Postprint is submitted to ZB.
Gene expression is regulated by multiple epigenetic mechanisms, which are coordinated in development and disease. However, current multiomics methods are frequently limited to one or two modalities at a time, making it challenging to obtain a comprehensive gene regulatory signature. Here, we describe a method—3D genome, RNA, accessibility and methylation sequencing (3DRAM-seq)—that simultaneously interrogates spatial genome organization, chromatin accessibility and DNA methylation genome-wide and at high resolution. We combine 3DRAM-seq with immunoFACS and RNA sequencing in cortical organoids to map the cell-type-specific regulatory landscape of human neural development across multiple epigenetic layers. Finally, we apply a massively parallel reporter assay to profile cell-type-specific enhancer activity in organoids and to functionally assess the role of key transcription factors for human enhancer activation and function. More broadly, 3DRAM-seq can be used to profile the multimodal epigenetic landscape in rare cell types and different tissues.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Transcription Factors; Cerebral Organoids; Dna Methylation; Open Chromatin; Binding; Genome; Organization; Principles; Landscape; Dynamics
ISSN (print) / ISBN 1465-7392
e-ISSN 1476-4679
Quellenangaben Volume: 12, Issue: 12, Pages: 1873-1883 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place Heidelberger Platz 3, Berlin, 14197, Germany
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)
Grants EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council)
Deutsche Forschungsgemeinschaft (German Research Foundation)