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Jesse Veenvliet and Marten Smidt from the Swammerdam Institute for Life Sciences demonstrate that certain epigenetic modifications play an important role in neuronal development.

In a recent study published in Proceedings in the National Academy of Sciences (PNAS) Jesse Veenvliet and Marten Smidt from the Swammerdam Institute for Life Sciences collaborated with the research group of Antonella Riccio to demonstrate that certain epigenetic modifications play an important role in neuronal development. Specific expression of genes is crucial in directing the specialisation of tissues such as the cerebral cortex during development. As a higher order level of regulation, dynamic epigenetic modifications of both DNA and histones (chromatine modifications) play a key role in mediating gene expression. Histone acetylases (HATs) and deacetylases (HDACs) are nuclear enzymes that maintain chromatin acetylation in balance, thereby contributing to activation and repression of genes.

The research group of Antonella Riccio (Laboratory for Molecular Cell Biology, University College London) showed in 2008 (Nott et al., Nature) that Nitric Oxide (NO) modifies HDAC2 by a post-translational modification of cysteines (so called S-Nitrosylation) and revealed that this results in HDAC2 dissociation from gene promoters, histone acetylation and consequent transcriptional activation of specific genes.

 

In their recent PNAS study, they show that HDAC2 S-Nitrosylation is necessary for neuronal morphology and radial neuron migration in the developing cortex. By genome-wide expression analysis of fluoresence activated cell sorted (FACS) neurons from embryonic cortices genetically modified through in-utero electroporation (IUE), techniques that are also part of the recently developed MSc Molecular Neuroscience at the UvA,  they identified genes regulated by HDAC2 S-Nitrosylation and showed that the regulation of ATP-dependent chromatin remodelling factor brahma (Brm) is critical during radial neuron migration in the developing cortex. Their findings link extracellular cues to chromatin remodelling in neurons and may have implications that extend beyond the mechanisms of cortical development, since Brm and NO signalling have been associated with schizophrenia.