Role of euchromatin histone methyltransferase 1 in network formation and modulation in vitro

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Intellectual Disability (ID) disorders share deficits in neuronal network formation, many converging onto the synapse. In particular, epigenetic regulators are disrupted in several forms of ID, such as MeCP2 in Rett Syndrome and FMR1 in Fragile X Syndrome. In this study we focus on the Kleefstra syndrome gene euchromatin histone methyltransferase 1, a modulator of post translational modifications involved in gene silencing. Here we investigated the influence of Ehmt1-deficiency on the neuronal network development in vitro. Neuronal activity is important for the development of the brain and is able to regulate and be regulated by activity-dependent genes. We found that knocking down EHMT1 affected formation of network bursts during the early phases of development. Using whole-cell electrophysiological recordings we found evidence that this phenotype is caused by a disruption in the balance between excitation and inhibition. Our data supports the requirement of EHMT1 in the early development of neuronal networks, underlying cognitive deficits in Kleefstra Syndrome patients.
Faculteit der Sociale Wetenschappen