title: Neuronal CTCF Is Necessary for Basal and Experience-Dependent Gene Regulation, Memory Formation, and Genomic Structure of BDNF and Arc.
abstract: CCCTC-binding factor (CTCF) is an organizer of higher-order chromatin structure and regulates gene expression. Genetic studies have implicated mutations in CTCF in intellectual disabilities. However, the role of CTCF-mediated chromatin structure in learning and memory is unclear. 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 thus suggests that CTCF-dependent gene expression regulation and genomic organization are regulators of learning and memory.
authors.affiliation: Faculty of Medicine, Bar Ilan University, Safed 13215, Israel.
authors.forename: Dev Sharan
authors.initials: DS
authors.lastname: Sams
authors.affiliation: Faculty of Medicine, Bar Ilan University, Safed 13215, Israel.
authors.forename: Stefano
authors.initials: S
authors.lastname: Nardone
authors.affiliation: Faculty of Medicine, Bar Ilan University, Safed 13215, Israel.
authors.forename: Dmitriy
authors.initials: D
authors.lastname: Getselter
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Dana
authors.initials: D
authors.lastname: Raz
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Moran
authors.initials: M
authors.lastname: Tal
authors.affiliation: Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel.
authors.forename: Prudhvi Raj
authors.initials: PR
authors.lastname: Rayi
authors.affiliation: Faculty of Natural Sciences, University of Haifa, Haifa 3498838, Israel.
authors.forename: Hanoch
authors.initials: H
authors.lastname: Kaphzan
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 5290002, Israel.
authors.forename: Ofir
authors.initials: O
authors.lastname: Hakim
authors.affiliation: Faculty of Medicine, Bar Ilan University, Safed 13215, Israel. Electronic address: evan.elliott@biu.ac.il.
authors.forename: Evan
authors.initials: E
authors.lastname: Elliott
mesh_terms: D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D001665:Binding Sites; D001921:Brain / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics* / Q000378:metabolism; D000076246:CCCTC-Binding Factor / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D003213:Conditioning, Psychological; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000378:metabolism; D005239:Fear; D005786:Gene Expression Regulation; D016678:Genome; D017774:Long-Term Potentiation; D008568:Memory / Q000502:physiology*; D008569:Memory Disorders / Q000235:genetics; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D013997:Time Factors
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D000076246:CCCTC-Binding Factor; D015820:Cadherins; D002843:Chromatin; D003598:Cytoskeletal Proteins; D009419:Nerve Tissue Proteins; C092069:activity regulated cytoskeletal-associated protein
keywords: 4C; BDNF; CTCF; arc; chromatin; genomic organization; high order; learning; memory