An amino terminal phosphorylation motif regulates intranuclear compartmentalization of Olig2 in neural progenitor cells

J Neurosci. 2014 Jun 18;34(25):8507-18. doi: 10.1523/JNEUROSCI.0309-14.2014.

Abstract

The bHLH transcription factor Olig2 is expressed in cycling neural progenitor cells but also in terminally differentiated, myelinating oligodendrocytes. Sustained expression of Olig2 is counterintuitive because all known functions of the protein in expansion of neural progenitors and specification of oligodendrocyte progenitors are completed with the formation of mature white matter. How are the biological functions of Olig2 suppressed in terminally differentiated oligodendrocytes? In previous studies, we have shown that a triple serine motif in the amino terminus of Olig2 is phosphorylated in cycling neural progenitors but not in their differentiated progeny. We now show that phosphorylation of the triple serine motif regulates intranuclear compartmentalization of murine Olig2. Phosphorylated Olig2 is preferentially localized to a transcriptionally active "open" chromatin compartment together with coregulator proteins essential for regulation of gene expression. Unphosphorylated Olig2, as seen in mature white matter, is localized mainly within a transcriptionally inactive, chromatin fraction characterized by condensed and inaccessible DNA. Of special note is the observation that the p53 tumor suppressor protein is confined to the open chromatin fraction. Proximity ligation assays show that phosphorylation brings Olig2 within 30 nm of p53 within the open chromatin compartment. The data thus shed light on previously noted promitogenic functions of phosphorylated Olig2, which reflect, at least in part, an oppositional relationship with p53 functions.

Keywords: NuRD complex; Olig2; bHLH; intranuclear localization; p53; phosphorylation.

Publication types

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

MeSH terms

  • Amino Acid Motifs / physiology
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism*
  • Basic Helix-Loop-Helix Transcription Factors / physiology*
  • Cell Nucleus / chemistry*
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism*
  • Cells, Cultured
  • Female
  • Male
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Nerve Tissue Proteins / physiology*
  • Neural Stem Cells / chemistry*
  • Neural Stem Cells / metabolism*
  • Oligodendrocyte Transcription Factor 2
  • Phosphorylation / genetics
  • Pregnancy

Substances

  • Basic Helix-Loop-Helix Transcription Factors
  • Nerve Tissue Proteins
  • Olig2 protein, mouse
  • Oligodendrocyte Transcription Factor 2