Zbtb48 is a regulator of Mtfp1 expression in zebrafish

TL;DR

This study shows that Zbtb48 regulates Mtfp1 in zebrafish, similar to its role in humans, but does not affect telomere length or cause visible abnormalities.

Contribution

The study demonstrates evolutionary conservation of Zbtb48's regulatory role on Mtfp1 in zebrafish.

Findings

Zbtb48−/− zebrafish mutants show downregulation of mtfp1 at mRNA and protein levels.

Mtfp1 downregulation is observed in the ovaries and testes of zbtb48−/− mutants.

Zbtb48 shows low expression in most tissues but is active in germline stem cells and gametocytes.

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−/− zebrafish line via CRISPR‒Cas genome editing. The zbtb48−/− 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−/− 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−/− mutants and in the testes of both 40 dpf and 10.5-month-old zbtb48−/− mutants.

The regulation of Mtfp1 by the transcription factor Zbtb48 is evolutionary conserved within vertebrates.

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