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

ABSTRACT: Gene expression is regulated by multiple epigenetic mechanisms, which are coordinated in development and disease. However, current multiomic 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 novel approach, 3DRAM-seq, which simultaneously interrogates spatial genome organization, chromatin accessibility, DNA methylation genome-wide and at high resolution. We combine 3DRAM-seq with immunoFACS and RNA-seq 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 (MPRA) to profile cell-type-specific enhancer activity in organoids and 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.

ORGANISM(S): Mus musculus Escherichia coli Homo sapiens

PROVIDER: GSE211736 | GEO | 2023/08/23

REPOSITORIES: GEO

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