Zbtb48 is a regulator of Mtfp1 expression in zebrafish

ZBTB48 (also known as TZAP) is a transcription factor that has previously been reported to bind to telomeres and act as a negative regulator of telomere length in human cell lines. To explore whether transcription factor activity and telomere length regulation are conserved at the organismal level in vertebrates, we generate a zbtb48<sup>-/-</sup> zebrafish line via CRISPR‒Cas genome editing. The zbtb48<sup>-/-</sup> mutants display no obvious physical or behavioral abnormalities in the first two generations. We find no statistically significant changes in telomere length in first-generation adults. However, for the gene regulatory aspect of Zbtb48, similar to that in human cancer cell lines, we observe downregulation of mtfp1 at both the mRNA and protein levels in the zbtb48<sup>-/-</sup> mutants. This suggests that mtfp1 is an evolutionarily conserved regulatory target of Zbtb48. Further investigation of the spatiotemporal expression of zbtb48 in previously published zebrafish data reveals low transcript expression in diverse tissues, except in germline stem cells and gametocytes of the gonads. Notably, Mtfp1 protein downregulation is detected in the ovaries of 40 dpf zbtb48<sup>-/-</sup> mutants and in the testes of both 40 dpf and 10.5-month-old zbtb48<sup>-/-</sup> mutants.

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Publication Details

Journal
Communications Biology
Published
2025-02-22
DOI
https://doi.org/10.1038/s42003-025-07666-z
Primary Topic
CRISPR and Genetic Engineering
Type
article
Field-Weighted Citation Impact
0.00

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article

Zbtb48 is a regulator of Mtfp1 expression in zebrafish

Falk Butter, René F. Ketting, Naz Şerifoğlu, Albert Fradera-Sola et al.
Communications Biology
CRISPR and Genetic Engineering
article

Zbtb48 is a regulator of Mtfp1 expression in zebrafish

Falk Butter, René F. Ketting, Naz Şerifoğlu, Albert Fradera-Sola, Nadine Wittkopp, Miguel Godinho Ferreira, Soon Pang Goh
article en

Abstract

ZBTB48 (also known as TZAP) is a transcription factor that has previously been reported to bind to telomeres and act as a negative regulator of telomere length in human cell lines. To explore whether transcription factor activity and telomere length regulation are conserved at the organismal level in vertebrates, we generate a zbtb48<sup>-/-</sup> zebrafish line via CRISPR‒Cas genome editing. The zbtb48<sup>-/-</sup> mutants display no obvious physical or behavioral abnormalities in the first two generations. We find no statistically significant changes in telomere length in first-generation adults. However, for the gene regulatory aspect of Zbtb48, similar to that in human cancer cell lines, we observe downregulation of mtfp1 at both the mRNA and protein levels in the zbtb48<sup>-/-</sup> mutants. This suggests that mtfp1 is an evolutionarily conserved regulatory target of Zbtb48. Further investigation of the spatiotemporal expression of zbtb48 in previously published zebrafish data reveals low transcript expression in diverse tissues, except in germline stem cells and gametocytes of the gonads. Notably, Mtfp1 protein downregulation is detected in the ovaries of 40 dpf zbtb48<sup>-/-</sup> mutants and in the testes of both 40 dpf and 10.5-month-old zbtb48<sup>-/-</sup> mutants.

Communications BiologyVol. 8(1)
Centre National de la Recherche Scientifique (FR), Friedrich-Loeffler-Institut (DE), Inserm (FR), Université Côte d'Azur (FR), Institut de Recherche sur le Cancer et le Vieillissement de Nice (FR), Institute of Molecular Biology (DE)
Deutsche Forschungsgemeinschaft
Openalex Percentile: Top 97%
CRISPR and Genetic Engineering
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Zbtb48 is a regulator of Mtfp1 expression in zebrafish — Falk Butter, René F. Ketting, et al. · Communications Biology (2025) | TGRS Research Map | TGRS