Satb2 determines miRNA expression and long-term memory in the adult central nervous system

Elife. 2016 Nov 29:5:e17361. doi: 10.7554/eLife.17361.

Abstract

SATB2 is a risk locus for schizophrenia and encodes a DNA-binding protein that regulates higher-order chromatin configuration. In the adult brain Satb2 is almost exclusively expressed in pyramidal neurons of two brain regions important for memory formation, the cerebral cortex and the CA1-hippocampal field. Here we show that Satb2 is required for key hippocampal functions since deletion of Satb2 from the adult mouse forebrain prevents the stabilization of synaptic long-term potentiation and markedly impairs long-term fear and object discrimination memory. At the molecular level, we find that synaptic activity and BDNF up-regulate Satb2, which itself binds to the promoters of coding and non-coding genes. Satb2 controls the hippocampal levels of a large cohort of miRNAs, many of which are implicated in synaptic plasticity and memory formation. Together, our findings demonstrate that Satb2 is critically involved in long-term plasticity processes in the adult forebrain that underlie the consolidation and stabilization of context-linked memory.

Keywords: LTP; chromatin; chromosomes; genes; long-term memory; miRNA; mouse; neuroscience; synaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Gene Expression Regulation*
  • Gene Knockout Techniques
  • Hippocampus / physiology*
  • Matrix Attachment Region Binding Proteins / genetics
  • Matrix Attachment Region Binding Proteins / metabolism*
  • Memory, Long-Term*
  • Mice
  • Mice, Knockout
  • MicroRNAs / biosynthesis*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*

Substances

  • Matrix Attachment Region Binding Proteins
  • MicroRNAs
  • SATB2 protein, mouse
  • Transcription Factors