Neuronal CTCF Is Necessary for Basal and Experience-Dependent Gene Regulation, Memory Formation, and Genomic Structure of BDNF and Arc

Cell Rep. 2016 Nov 22;17(9):2418-2430. doi: 10.1016/j.celrep.2016.11.004.


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.

Keywords: 4C; BDNF; CTCF; arc; chromatin; genomic organization; high order; learning; memory.

MeSH terms

  • Adenoviridae / metabolism
  • Animals
  • Behavior, Animal
  • Binding Sites
  • Brain / metabolism
  • Brain-Derived Neurotrophic Factor / genetics*
  • Brain-Derived Neurotrophic Factor / metabolism
  • CCCTC-Binding Factor / metabolism*
  • Cadherins / metabolism
  • Chromatin / metabolism
  • Conditioning, Psychological
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / metabolism
  • Fear
  • Gene Expression Regulation*
  • Genome*
  • Long-Term Potentiation
  • Memory / physiology*
  • Memory Disorders / genetics
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / metabolism
  • Neurons / metabolism*
  • Time Factors


  • Brain-Derived Neurotrophic Factor
  • CCCTC-Binding Factor
  • Cadherins
  • Chromatin
  • Cytoskeletal Proteins
  • Nerve Tissue Proteins
  • activity regulated cytoskeletal-associated protein