Genes 2 Brains 2 Mind 2 Me

Image via Wikipedia Siming Shen et al., in their paper, “Age-dependent epigenetic control of differentiation inhibitors is critical for remyelination efficiency“ provide insight on basic mechanisms of myelination. While myelination (think of it as the plastic insulation on copper electrical wires) makes normally developing neural networks much more efficient, it has a way of inhibiting the re-development and repair of mature neural circuits. The research team shows that recruitment of histone deacetylases (HDACs) is rather inefficient in mature oligodendrocytes precursor cells (the cells that adhere to bare neuronal axons and form the insulating myelin-rich sheath) in contrast to younger cells which differentiate readily. HDAC1 and HDAC2 are shown to down-regulate of Hes5 and Sox2, which have previously been implicated in blocking the differentiation of stem cells to oligodendrocytes. Here, the term ‘epigenetic’ refers to the mechanism of gene regulation – not by way of transcription factors binding to specific sequences – but rather, by factors being sterically blocked from binding by the 3-dimensional superstructure of the chromosome that occurs when histone proteins are deacetylated. The team suggests that as the brain ages, it becomes more difficult to recruit HDAC1,2 to the promoters needed to shut down the expression of the differentiation inhibitors. The results pose a confound for the certain applications of inhibitors of histone deacetylases (HDACi) which have demonstrated anti-tumor activity – but may – as suggested by this article – have negative consequences on brain repair processes.