Remote memory and cortical synaptic plasticity require neuronal CCCTC-binding factor (CTCF)

Somi Kim, Nam Kyung Yu, Kyu Won Shim, Ji Il Kim, Hyopil Kim, Dae Hee Han, Ja Eun Choi, Seung Woo Lee, Dong Il Choi, Myung Won Kim, Dong Sung Lee, Kyungmin Lee, Niels Galjart, Yong Seok Lee, Jae Hyung Lee, Bong Kiun Kaang

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)


The molecular mechanism of long-term memory has been extensively studied in the context of the hippocampus-dependent recent memory examined within several days. However, months-old remote memory maintained in the cortex for long-term has not been investigated much at the molecular level yet. Various epigenetic mechanisms are known to be important for long-term memory, but how the 3D chromatin architecture and its regulator molecules contribute to neuronal plasticity and systems consolidation is still largely unknown. CCCTC-binding factor (CTCF) is an 11-zinc finger protein well known for its role as a genome architecture molecule. Male conditional knock-out mice in which CTCF is lost in excitatory neurons during adulthood showed normal recent memory in the contextual fear conditioning and spatial water maze tasks. However, they showed remarkable impairments in remote memory in both tasks. Underlying the remote memory-specific phenotypes, we observed that female CTCF conditional knock-out mice exhibit disrupted cortical LTP, but not hippocampal LTP. Similarly, we observed that CTCF deletion in inhibitory neurons caused partial impairment of remote memory. Through RNA sequencing, we observed that CTCF knockdown in cortical neuron culture caused altered expression of genes that are highly involved in cell adhesion, synaptic plasticity, and memory. These results suggest that remote memory storage in the cortex requires CTCF-mediated gene regulation in neurons, whereas recent memory formation in the hippocampus does not.

Original languageEnglish
Pages (from-to)5042-5052
Number of pages11
JournalJournal of Neuroscience
Issue number22
Publication statusPublished - 30 May 2018


  • 3D genome architecture
  • CTCF
  • Cortical plasticity
  • Remote memory
  • Systems consolidation


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