Zbtb34 promotes embryonic stem cell proliferation by elongating telomere length

Aging (Albany NY). 2022 Sep 12;14(17):7126-7136. doi: 10.18632/aging.204285. Epub 2022 Sep 12.

Abstract

Zbtb34 is a novel zinc finger protein, which is revealed by biological software analysis to have 3 zinc fingers, but its functions remain unknown. In this study, mouse Zbtb34 cDNA was amplified by PCR and inserted into the plasmid pEGFP-N1 to generate Zbtb34-EGFP fusion protein. The upregulation of Zbtb34 in mouse embryonic stem cells promoted telomere elongation and increased cell proliferation. In order to understand the above phenomena, the telomere co-immunoprecipitation technique was employed to investigate the relationship between Zbtb34 and telomeres. The results indicated that Zbtb34 could bind to the DNA sequences of the telomeres. Alanine substitution of the third zinc finger abolished such binding. Since Pot1 is the only protein binding to the single-stranded DNA at the end of the telomeres, we further investigated the relationship between Zbtb34 and Pot1. The results revealed that the upregulation of Zbtb34 decreased the binding of Pot1b to the telomeres. Through the upregulation of Pot1b, the binding of Zbtb34 to the telomeres was also reduced. In conclusion, we showed that the main biological function of Zbtb34 was to bind telomere DNA via its third ZnF, competing with Pot1b for the binding sites, resulting in telomere elongation and cell proliferation.

Keywords: Pot1b; Zbtb34; mouse embryonic stem cells; telomere; zinc finger.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alanine / genetics
  • Animals
  • Cell Proliferation
  • DNA
  • DNA, Complementary
  • DNA, Single-Stranded*
  • DNA-Binding Proteins / genetics
  • Embryonic Stem Cells / metabolism
  • Mice
  • Repressor Proteins* / metabolism
  • Shelterin Complex
  • Telomere / genetics
  • Telomere / metabolism
  • Telomere-Binding Proteins* / genetics
  • Telomere-Binding Proteins* / metabolism

Substances

  • Alanine
  • DNA
  • DNA, Complementary
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • POT1b protein, mouse
  • Repressor Proteins
  • Shelterin Complex
  • Telomere-Binding Proteins
  • Zbtb34 protein, mouse