RNA-seq of hippocampus from wild type and CTCF cko animals. Mus musculus

CTCF is an organizer of higher-order chromatin structure, and regulates gene expression. Genetic studies have implicated mutations in CTCF in intellectual disabilities. However, there is no knowledge of the role of CTCF-mediated chromatin structure in learning and memory. We show that depletion of CTCF in postmitotic neurons, or depletion in the hippocampus of adult mice through viral-mediated knockout, induces deficits in learning and memory. These deficits in learning and memory at the beginning of adulthood are correlated with impaired long term potentiation and reduced spine density, with no changes in basal synaptic transmission and dendritic morphogenesis and arborization. Cognitive disabilities are associated with downregulation of cadherin and learning-related genes. In addition, CTCF knockdown attenuates fear conditioning-induced hippocampal gene expression of key learning genes and loss of long-range interactions at the BDNF and Arc loci. This study identifies CTCF-dependent gene expression regulation and DNA structure as regulators of learning and memory. Overall design: 3 biological replicates of wild type and 3 biological replicates of CTCF cko mice