A Functional Role for the Epigenetic Regulator ING1 in Activity-induced Gene Expression in Primary Cortical Neurons

Neuroscience. 2018 Jan 15;369:248-260. doi: 10.1016/j.neuroscience.2017.11.018. Epub 2017 Nov 20.

Abstract

Epigenetic regulation of activity-induced gene expression involves multiple levels of molecular interaction, including histone and DNA modifications, as well as mechanisms of DNA repair. Here we demonstrate that the genome-wide deposition of inhibitor of growth family member 1 (ING1), which is a central epigenetic regulatory protein, is dynamically regulated in response to activity in primary cortical neurons. ING1 knockdown leads to decreased expression of genes related to synaptic plasticity, including the regulatory subunit of calcineurin, Ppp3r1. In addition, ING1 binding at a site upstream of the transcription start site (TSS) of Ppp3r1 depends on yet another group of neuroepigenetic regulatory proteins, the Piwi-like family, which are also involved in DNA repair. These findings provide new insight into a novel mode of activity-induced gene expression, which involves the interaction between different epigenetic regulatory mechanisms traditionally associated with gene repression and DNA repair.

Keywords: DNA repair; ING1; Piwi-like proteins; epigenetics; gene regulation; neuronal activation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Argonaute Proteins / metabolism
  • Calcium-Binding Proteins
  • Cells, Cultured
  • Cerebral Cortex / metabolism*
  • Epigenesis, Genetic*
  • Fibroblasts / metabolism
  • Gene Expression Regulation
  • Gene Knockdown Techniques
  • Humans
  • Inhibitor of Growth Protein 1 / genetics
  • Inhibitor of Growth Protein 1 / metabolism*
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice, Inbred C57BL
  • Muscle Proteins / metabolism
  • Neurons / metabolism*
  • RNA, Messenger / metabolism

Substances

  • Argonaute Proteins
  • Calcium-Binding Proteins
  • DSCR1 protein, mouse
  • Ing1 protein, mouse
  • Inhibitor of Growth Protein 1
  • Intracellular Signaling Peptides and Proteins
  • Muscle Proteins
  • Piwil1 protein, mouse
  • Piwil2 protein, mouse
  • RNA, Messenger