Phosphorylation State of ZFP24 Controls Oligodendrocyte Differentiation

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

doi:10.1016/j.celrep.2018.04.089

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

Department of Cell and Developmental Biology

Research output: Contribution to journal › Article › peer-review

19 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 language	American English
Pages (from-to)	2254-2263
Number of pages	10
Journal	Cell Reports
Volume	23
Issue number	8
DOIs	https://doi.org/10.1016/j.celrep.2018.04.089
State	Published - 22 May 2018

Bibliographical note

Funding Information:
We would like to thank Rejani B. Kunjamma, Ani Solanki, and Gloria Wright for their technical assistance. This work was supported by grants to B.P. from the Myelin Repair Foundation , the NIH ( R01NS067550 ), the National Multiple Sclerosis Society ( RG-1501-02797 ), and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation . S.I. and A.E. are supported by the Israel Science Foundation (ISF; grant 1361/14 ).

Publisher Copyright:
© 2018 The Author(s)

Keywords

CNS
chromatin
differentiation
myelination
oligodendrocytes
transcription
zinc finger

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10.1016/j.celrep.2018.04.089

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title = "Phosphorylation State of ZFP24 Controls Oligodendrocyte Differentiation",

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.",

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author = "Benayahu Elbaz and Aaker, {Joshua D.} and Sara Isaac and Anna Kolarzyk and Pedro Brugarolas and Amir Eden and Brian Popko",

note = "Funding Information: We would like to thank Rejani B. Kunjamma, Ani Solanki, and Gloria Wright for their technical assistance. This work was supported by grants to B.P. from the Myelin Repair Foundation , the NIH ( R01NS067550 ), the National Multiple Sclerosis Society ( RG-1501-02797 ), and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation . S.I. and A.E. are supported by the Israel Science Foundation (ISF; grant 1361/14 ). Publisher Copyright: {\textcopyright} 2018 The Author(s)",

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AU - Elbaz, Benayahu

AU - Aaker, Joshua D.

AU - Isaac, Sara

AU - Kolarzyk, Anna

AU - Brugarolas, Pedro

AU - Eden, Amir

AU - Popko, Brian

N1 - Funding Information: We would like to thank Rejani B. Kunjamma, Ani Solanki, and Gloria Wright for their technical assistance. This work was supported by grants to B.P. from the Myelin Repair Foundation , the NIH ( R01NS067550 ), the National Multiple Sclerosis Society ( RG-1501-02797 ), and the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation . S.I. and A.E. are supported by the Israel Science Foundation (ISF; grant 1361/14 ). Publisher Copyright: © 2018 The Author(s)

PY - 2018/5/22

Y1 - 2018/5/22

N2 - 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.

AB - 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.

KW - CNS

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KW - differentiation

KW - myelination

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DO - 10.1016/j.celrep.2018.04.089

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EP - 2263

JO - Cell Reports

JF - Cell Reports

IS - 8

ER -

Phosphorylation State of ZFP24 Controls Oligodendrocyte Differentiation

Abstract

Bibliographical note

Keywords

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