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

Dev Sharan Sams, Stefano Nardone, Dmitriy Getselter, Dana Raz, Moran Tal, Prudhvi Raj Rayi, Hanoch Kaphzan, Ofir Hakim, Evan Elliott

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2418-2430
Number of pages13
JournalCell Reports
Volume17
Issue number9
DOIs
StatePublished - 22 Nov 2016

Bibliographical note

Funding Information:
We would like to acknowledge and thank the Israel National Center for Personalized Medicine at the Weizmann Institute of Science, and particularly Dr. Gilgi Friedlander, for their work and great assistance in the sequencing and bioinformatics that are outlined in this manuscript. In addition, we would like to acknowledge the Bar Ilan University Faculty of Medicine Animal Facilities staff, including Dr. Roey Lahav. We thank Anita Impagliazzo for the artwork. This work is supported by the Israel Science Foundation (grant 1047/12 ).

Publisher Copyright:
© 2016 The Author(s)

Keywords

  • 4C
  • BDNF
  • CTCF
  • arc
  • chromatin
  • genomic organization
  • high order
  • learning
  • memory

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology (all)

Fingerprint

Dive into the research topics of 'Neuronal CTCF Is Necessary for Basal and Experience-Dependent Gene Regulation, Memory Formation, and Genomic Structure of BDNF and Arc'. Together they form a unique fingerprint.

Cite this