Department of Neurology, Center for Peripheral Neuropathy, University of Chicago, Chicago, IL 60637, USA.
Department of Cell and Developmental Biology, The Alexander Silberman Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem, Israel.
Cell Rep. 2018 May 22;23(8):2254-2263. doi: 10.1016/j.celrep.2018.04.089.
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.
锌指蛋白 ZFP24，以前称为 ZFP191，对少突胶质细胞成熟和中枢神经系统髓鞘形成至关重要。然而，ZFP24 控制这些过程的机制尚不清楚。我们证明 ZFP24 与靠近对少突胶质细胞分化和中枢神经系统髓鞘形成很重要的基因的保守 DNA 序列结合，并且我们表明这种结合增强了靶基因的表达。我们还证明 ZFP24 的 DNA 结合受磷酸化控制。不结合 DNA 的磷酸化 ZFP24 是少突胶质细胞祖细胞中的主要形式。随着这些细胞成熟为少突胶质细胞，非磷酸化、与 DNA 结合的形式积累。有趣的是，ZFP24 与转录因子 MYRF、SOX10 和 OLIG2 的基因组结合位点重叠，这些转录因子已知可控制少突胶质细胞分化。我们的研究结果提供了一种机制，通过该机制，ZFP24 的去磷酸化介导其与对少突胶质细胞成熟很重要的基因的调控区域结合，控制其表达，从而调节少突胶质细胞分化和中枢神经系统髓鞘形成。
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