BRG1 establishes the neuroectodermal chromatin landscape to restrict dorsal cell fates.
Jackson A HoffmanGinger W MuseLee F LangerA Isabella PattersonIsabella GandaraJames M WardTrevor K ArcherPublished in: Science advances (2024)
Cell fate decisions are achieved with gene expression changes driven by lineage-specific transcription factors (TFs). These TFs depend on chromatin remodelers including the Brahma-related gene 1 (BRG1)-associated factor (BAF) complex to activate target genes. BAF complex subunits are essential for development and frequently mutated in cancer. Thus, interrogating how BAF complexes contribute to cell fate decisions is critical for human health. We examined the requirement for the catalytic BAF subunit BRG1 in neural progenitor cell (NPC) specification from human embryonic stem cells. During the earliest stages of differentiation, BRG1 was required to establish chromatin accessibility at neuroectoderm-specific enhancers. Depletion of BRG1 dorsalized NPCs and promoted precocious neural crest specification and enhanced neuronal differentiation. These findings demonstrate that BRG1 mediates NPC specification by ensuring proper expression of lineage-specific TFs and appropriate activation of their transcriptional programs.
Keyphrases
- cell fate
- gene expression
- transcription factor
- genome wide
- human health
- dna damage
- genome wide identification
- risk assessment
- embryonic stem cells
- dna methylation
- single cell
- endothelial cells
- poor prognosis
- copy number
- spinal cord
- neuropathic pain
- squamous cell carcinoma
- climate change
- dna binding
- bone marrow
- long non coding rna
- induced pluripotent stem cells
- protein kinase
- crystal structure
- heat shock