This symposium explores the many ways by which the genome is regulated in the brain in order to support neural function and plasticity. The extraordinary complexity of the brain places unique demands on the genome: How are several hundreds of different neural types specified by the same genetic instructions? Does the genome provide information that guides their connectivity? How is neural activity regulated by and how does it affect genome output? We will explore these fundamental questions from the standpoint of transcriptional regulation and chromatin-based processes, including but not limited to histone marks and variants, chromatin topology and folding, coding and noncoding RNAs, transposable elements, and DNA modifications. The conference aims to bring together neuroscientists and experts in genome regulation. It will cover a broad range of experimental approaches and model systems, from biochemistry to single-cell genomics, from worms to human organoids. Overall, the conference will address the impact of genome regulation on unique features of the brain — its excitable nature, exquisite response to the environment and parallel processing capacity — with the longer-term vision of understanding how defective genome regulation can give rise to brain disease.