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Publication : Transcription factor Zfp276 drives oligodendroglial differentiation and myelination by switching off the progenitor cell program.

First Author  Aberle T Year  2022
Journal  Nucleic Acids Res Volume  50
Issue  4 Pages  1951-1968
PubMed ID  35137157 Mgi Jnum  J:324574
Mgi Id  MGI:6887037 Doi  10.1093/nar/gkac042
Citation  Aberle T, et al. (2022) Transcription factor Zfp276 drives oligodendroglial differentiation and myelination by switching off the progenitor cell program. Nucleic Acids Res 50(4):1951-1968
abstractText  In oligodendrocytes of the vertebrate central nervous system a complex network of transcriptional regulators is required to ensure correct and timely myelination of neuronal axons. Here we identify Zfp276, the only mammalian ZAD-domain containing zinc finger protein, as a transcriptional regulator of oligodendrocyte differentiation and central myelination downstream of Sox10. In the central nervous system, Zfp276 is exclusively expressed in mature oligodendrocytes. Oligodendroglial deletion of Zfp276 led to strongly reduced expression of myelin genes in the early postnatal mouse spinal cord. Retroviral overexpression of Zfp276 in cultured oligodendrocyte precursor cells induced precocious expression of maturation markers and myelin genes, further supporting its role in oligodendroglial differentiation. On the molecular level, Zfp276 directly binds to and represses Sox10-dependent gene regulatory regions of immaturity factors and functionally interacts with the transcriptional repressor Zeb2 to enable fast transition of oligodendrocytes to the myelinating stage.
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