# ZFP24 Control of the myelination program of oligodendrocytes

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $345,625

## Abstract

ABSTRACT
The zinc finger protein 24 (ZFP24) is required for oligodendrocyte maturation and CNS myelination. ZFP24
binds to a consensus DNA sequence in proximity to genes important for oligodendrocyte differentiation, and
this binding enhances target gene expression. ZFP24 contains four C2H2 zinc-finger domains that are
interspersed by three conserved linkers. ZFP24 DNA binding is controlled by phosphorylation of the conserved
linkers: phosphorylated ZFP24, which does not bind DNA, is the predominant form in oligodendrocyte
progenitor cells (OPCs). As these cells mature into oligodendrocytes, the non-phosphorylated, DNA-binding
form accumulates. Our findings indicate that changes to ZFP24 phosphorylation control its binding to
regulatory regions of genes important for oligodendrocyte maturation, controls their expression, and thereby
regulates oligodendrocyte differentiation and CNS myelination. Therefore, it is critical to identify the kinase(s)
and phosphatase(s) responsible for controlling the functional status of ZFP24. In the first aim we propose two
distinct unbiased screening approaches toward the identification of the ZFP24 kinase(s). We will also examine
the effect of inhibition of the identified kinase(s) on ZFP24 phosphorylation, ZFP24 activity, oligodendrocyte
maturation and myelin related gene expression. The second aim focuses on identifying the phosphatase(s)
that de-phosphorylates ZFP24 to generate the functional transcriptional factor. We will use a candidate
phosphatase screen, as well as an unbiased screen to identify these ZFP24 phosphatases. We will also
examine the effect of inhibition of the identified phosphatase(s) on ZFP24 activity, ZFP24 phosphorylation,
oligodendrocyte maturation and myelin related gene expression. In the third aim we will characterize
phosphorylation intermediate isoforms of ZFP24. We have identified ZFP24 isoforms in which one, two or all
three potential phosphorylation sites in the conserved ZFP24 linker domains are phosphorylated in cultured
oligodendrocyte lineage cells. Currently it is unclear whether these are non-functional, transitional ZFP24
isoforms, or if these forms are important intermediates with unique functions in oligodendrocyte development.
Therefore, in the third aim we will study the half-life of the intermediate forms and determine if the distinct
isoforms have unique functions in oligodendrocyte development. Aim four is devoted to the elucidation of the
potential role that ZFP24 plays in the CNS of adult animals, including myelin maintenance and remyelination.
We also propose to generate a new mouse model that will allow for the inducible expression of the active, non-
phosphorylated, form of ZFP24 in OPCs. This model will be used to test the potential ability of the active form
of ZFP24 to enhance remyelination. Overall, the studies described here will provide a more detailed
understanding of the role that ZFP24 phosphorylation plays in oligodendrocyte maturation, CNS myelination...

## Key facts

- **NIH application ID:** 9897289
- **Project number:** 2R01NS067550-06A1
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Benayahu Elbaz-Eilon
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $345,625
- **Award type:** 2
- **Project period:** 2009-09-30 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9897289

## Citation

> US National Institutes of Health, RePORTER application 9897289, ZFP24 Control of the myelination program of oligodendrocytes (2R01NS067550-06A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9897289. Licensed CC0.

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