The Polycomb complex: a key regulator in altered neurogenesis resulting from early-life stress?
Summary
Exposure to stress during a critical period in childhood is associated with cognitive and emotional deficits in adulthood, underlied by structural and functional changes in the hippocampus. A disturbed process of adult neurogenesis in the hippocampus, which is under tight regulation of epigenetic mechanisms, seems to cause these disorders. Polycomb proteins are important epigenetic mediators in early development and play a critical role in neuronal differentiation as well. Polycomb complexes silence their target genes via methylating Lys27 on histone H3. In cortical development, Polycomb acts as spatiotemporal switch between proliferation and differentiation. In adult neurogenesis, the exact function of Polycomb proteins is not clarified yet, although it is clear that interactions with other epigenetic mechanisms are crucial for their executive roles. On the effect of early-life stress on Polycomb proteins, just a few studies have appeared yet. Most promising features for future studies to focus on would be: the downregulation of Polycomb protein BMI1 as a result of early-life stress; Polycomb complexes regulating the genes encoding the glucocorticoid receptor and corticotropin releasing hormone; and interaction of glucocorticoids with the mitogen- and stress-activated kinases 1 and 2 which replace Polycomb proteins from the DNA. An interaction between the epigenetic mechanisms of Polycomb regulation and DNA methylation seems plausible, although the level of complexity of Polycomb interference remains an evident question.