Format

Send to

Choose Destination
See comment in PubMed Commons below
J Neurosci. 2014 Jun 18;34(25):8507-18. doi: 10.1523/JNEUROSCI.0309-14.2014.

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

Author information

1
Department of Neurobiology, Harvard Medical School and Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215.
2
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, Massachusetts 02215.
3
Departments of Biological Chemistry and Molecular Pharmacology, Harvard Medical School and Cancer Biology, Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, Massachusetts 02215.
4
Department of Neurosurgery, Barrow Brain Tumor Research Center, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013.
5
Departments of Pediatrics and Neurological Surgery, Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, California 94143, and.
6
Department of Neurobiology, Harvard Medical School and Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, Charles_stiles@dfci.harvard.edu Shwetal.Mehta@dignityhealth.org.
7
Department of Neurosurgery, Barrow Brain Tumor Research Center, Barrow Neurological Institute, St. Joseph's Hospital and Medical Center, Phoenix, Arizona 85013 Charles_stiles@dfci.harvard.edu Shwetal.Mehta@dignityhealth.org.

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

PMID:
24948806
PMCID:
PMC4061392
DOI:
10.1523/JNEUROSCI.0309-14.2014
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Support Center