Histone bivalency regulates the timing of cerebellar granule cell development.
Kärt MätlikEve-Ellen GovekMatthew R PaulC David AllisMary E HattenPublished in: Genes & development (2023)
Developing neurons undergo a progression of morphological and gene expression changes as they transition from neuronal progenitors to mature neurons. Here we used RNA-seq and H3K4me3 and H3K27me3 ChIP-seq to analyze how chromatin modifications control gene expression in a specific type of CNS neuron: the mouse cerebellar granule cell (GC). We found that in proliferating GC progenitors (GCPs), H3K4me3/H3K27me3 bivalency is common at neuronal genes and undergoes dynamic changes that correlate with gene expression during migration and circuit formation. Expressing a fluorescent sensor for bivalent domains revealed subnuclear bivalent foci in proliferating GCPs. Inhibiting H3K27 methyltransferases EZH1 and EZH2 in vitro and in organotypic cerebellar slices dramatically altered the expression of bivalent genes, induced the down-regulation of migration-related genes and up-regulation of synaptic genes, inhibited glial-guided migration, and accelerated terminal differentiation. Thus, histone bivalency is required to regulate the timing of the progression from progenitor cells to mature neurons.
Keyphrases
- gene expression
- single cell
- rna seq
- dna methylation
- genome wide
- high throughput
- spinal cord
- bioinformatics analysis
- poor prognosis
- long non coding rna
- genome wide identification
- cell therapy
- long noncoding rna
- genome wide analysis
- high glucose
- dna damage
- transcription factor
- gas chromatography
- binding protein
- quantum dots
- high resolution
- mass spectrometry
- prefrontal cortex
- bone marrow