Epigenetic regulation via covalent histone modifications plays an important role in dictating developmental processes and cell fate determination. It complements to genetic information and provides additional regulatory mechanisms in response to fast changing cellular and organismal environment during development. Recent studies show that mutations in histone modifying enzymes often skew the normal development ?roadmap? and consequently lead to human diseases. PRDM16 plays an important role in maintaining homeostasis of multiple adult stem cells including neural stem cells. Importantly, Prdm16 deletion in mice leads to multiple brain defects including microcephaly, disrupted cerebral cortex and agenesis of the corpus callosum. However, it remains unclear how PRDM16 regulate functions of neural progenitor cells and how its deletion leads to disruption of normal neurogenesis. We have recently found that PRDM16 is a histone methyltransferase that methylate histone H3. This finding links PRDM16 deletion to deregulation of epigenetic modifications in neural stem cells, which play essential roles in define transcription circuitries in stem cells that define cellular identity.
The epigenetic mechanisms link seemingly disparate fields of science and medicine, such as development, degeneration, inflammation, infection, stem cell biology, and cancer. Recurrent mutations in epigenetic modulators have been identified in a variety of developmental disorders. The goal of this work is to understand the molecular basis of epigenetic regulation in neural stem cell differentiation and brain development. It aims toaddress fundamental questions in these processes and shed light on potential targets that may be useful for early intervention.
|Khoa, Le Tran Phuc; Dou, Yali (2017) Phosphoproteomics links glycogen synthase kinase-3 to RNA splicing. J Biol Chem 292:18256-18257|