Phosphorylation State of ZFP24 Controls Oligodendrocyte Differentiation

Benayahu Elbaz, Joshua D. Aaker, Sara Isaac, Anna Kolarzyk, Pedro Brugarolas, Amir Eden, Brian Popko*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Zinc finger protein ZFP24, formerly known as ZFP191, is essential for oligodendrocyte maturation and CNS myelination. Nevertheless, the mechanism by which ZFP24 controls these processes is unknown. We demonstrate that ZFP24 binds to a consensus DNA sequence in proximity to genes important for oligodendrocyte differentiation and CNS myelination, and we show that this binding enhances target gene expression. We also demonstrate that ZFP24 DNA binding is controlled by phosphorylation. Phosphorylated ZFP24, which does not bind DNA, is the predominant form in oligodendrocyte progenitor cells. As these cells mature into oligodendrocytes, the non-phosphorylated, DNA-binding form accumulates. Interestingly, ZFP24 displays overlapping genomic binding sites with the transcription factors MYRF, SOX10, and OLIG2, which are known to control oligodendrocyte differentiation. Our findings provide a mechanism by which dephosphorylation of ZFP24 mediates its binding to regulatory regions of genes important for oligodendrocyte maturation, controls their expression, and thereby regulates oligodendrocyte differentiation and CNS myelination. Elbaz et al. describe a mechanism by which dephosphorylation of the zinc finger protein ZFP24 mediates its binding to the regulatory regions of genes important for oligodendrocyte maturation, controls their expression, and thereby regulates oligodendrocyte differentiation and CNS myelination.

Original languageEnglish (US)
Pages (from-to)2254-2263
Number of pages10
JournalCell reports
Volume23
Issue number8
DOIs
StatePublished - May 22 2018

Keywords

  • CNS
  • chromatin
  • differentiation
  • myelination
  • oligodendrocytes
  • transcription
  • zinc finger

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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