martedì 19 giugno 2018, ore 14:00, aula 2025, edificio U3.
Ramon Y Birnbaum, Department of Life Sciences, the Ben-Gurion University at the Negev, Israel
Epilepsy is one of the most common neurological disorders. It is a complex and heterogeneous disorder which makes it difficult to precisely diagnose and provide effective treatment. A major and underexplored cause of epilepsy could be mutations in gene regulatory elements, such as enhancers. Disruption of these elements, and subsequently of the gene regulatory networks that are involved in brain development, can lead to early onset of epilepsy, such as infantile spasms (IS). This type of epilepsy is linked to an imbalance between glutamatergic projection neurons (excitatory) and GABAergic interneurons (inhibitory). With many IS-associated genes being important for forebrain inhibitory GABAergic interneuron development and function, disruption of the gene regulatory networks in these inhibitory interneurons could lead to IS. Using chromatin immuneprecipitation followed by deep sequencing (ChIP-Seq) with enhancer marks (H3K27ac, RNAPoll2), we identified transcriptional enhancer candidates during differentiation of human embryonic stem cells into inhibitory interneurons. Using RNA-seq, we determined the expression of IS-associated genes and their potential regulated enhancers. In addition, several candidate sequences showed spatiotemporal neuronal activity with high similarity to their potential regulated genes using zebrafish transgenic enhancer assays. Combined, this study provides a novel dataset of the regulatory landscape that controls the spatiotemporal gene expression during inhibitory interneurons and highlights genomic regions in the human genome where mutations could lead to IS and other epilepsies.
about Dr. Ramon Birnbaum
Ospite: Antonella Ronchi