PRMT1 and PRMT8 Regulate Retinoic Acid‐Dependent Neuronal Differentiation with Implications to Neuropathology

摘要: Retinoids are morphogens and have been implicated in cell fate commitment of embryonic stem cells (ESCs) to neurons. Their effects mediated by RAR RXR nuclear receptors. However, transcriptional cofactors required for gene-specific retinoid signaling not known. Here we show that protein arginine methyl transferase (PRMT) 1 8 key roles determining regulated gene expression cellular specification a multistage neuronal differentiation model murine ESCs. PRMT1 acts as selective modulator, providing the with mechanism reduce potency signals on regulatory "hotspots." PRMT8 is receptor target itself type specific coactivator at later stages differentiation. Lack either them leads reduced methylation, dysregulated expression, altered activity. Importantly, depletion results distinct set genes, including markers gliomagenesis. almost entirely absent human glioblastoma tissues. We propose serve rheostat determine context-dependent manner might also be relevant development brain malignancy.