Histone bivalency regulates the timing of cerebellar granule cell development.
Kärt MätlikEve-Ellen GovekMatthew R PaulC David AllisMary E HattenPublished in: bioRxiv : the preprint server for biology (2023)
Developing neurons undergo a progression of morphological and gene expression changes as they transition from neuronal progenitors to mature, multipolar neurons. Here we use 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 find 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 H3K4me3 and H3K27me3 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 and induced the downregulation of migration-related genes and upregulation 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
- poor prognosis
- signaling pathway
- cell proliferation
- long non coding rna
- bioinformatics analysis
- genome wide identification
- cell therapy
- stem cells
- diabetic rats
- high glucose
- spinal cord injury
- quantum dots
- long noncoding rna
- living cells
- high resolution
- mesenchymal stem cells
- blood brain barrier
- oxidative stress
- gas chromatography
- bone marrow
- liquid chromatography
- label free