Joint epigenome profiling reveals cell-type-specific gene regulatory programmes in human cortical organoids.
Nat Cell Biol
; 25(12): 1873-1883, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37996647
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cromatina
/
Epigenoma
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article