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

Aberle T, Piefke S, Hillgärtner S, Tamm ER, Wegner M, Küspert M (2022)

Publication Type: Journal article

Publication year: 2022

Journal

Nucleic Acids Research Oxford University Press

Book Volume: 50

Pages Range: 1951-1968

Journal Issue: 4

DOI: 10.1093/nar/gkac042

Abstract

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.

Authors with CRIS profile

Tim Aberle Lehrstuhl für Biochemie und Pathobiochemie Sandra Piefke Lehrstuhl für Biochemie und Pathobiochemie Simone Hillgärtner Lehrstuhl für Biochemie und Pathobiochemie Michael Wegner Lehrstuhl für Biochemie und Pathobiochemie Melanie Küspert Lehrstuhl für Biochemie und Pathobiochemie

Involved external institutions

Universität Regensburg DE Germany (DE)

How to cite

APA:

Aberle, T., Piefke, S., Hillgärtner, S., Tamm, E.R., Wegner, M., & Küspert, M. (2022). Transcription factor Zfp276 drives oligodendroglial differentiation and myelination by switching off the progenitor cell program. Nucleic Acids Research, 50(4), 1951-1968. https://dx.doi.org/10.1093/nar/gkac042

MLA:

Aberle, Tim, et al. "Transcription factor Zfp276 drives oligodendroglial differentiation and myelination by switching off the progenitor cell program." Nucleic Acids Research 50.4 (2022): 1951-1968.

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