ZBTB10 binds the telomeric variant repeat TTGGGG and interacts with TRF2

Nucleic Acids Res. 2019 Feb 28;47(4):1896-1907. doi: 10.1093/nar/gky1289.

Abstract

Telomeres are nucleoprotein structures at the ends of linear chromosomes and present an essential feature for genome integrity. Vertebrate telomeres usually consist of hexameric TTAGGG repeats, however, in cells that use the alternative lengthening of telomeres (ALT) mechanism, variant repeat sequences are interspersed throughout telomeres. Previously, it was shown that NR2C/F transcription factors bind to TCAGGG variant repeats and contribute to telomere maintenance in ALT cells. While specific binders to other variant repeat sequences have been lacking to date, we here identify ZBTB10 as the first TTGGGG-binding protein and demonstrate direct binding via the two zinc fingers with affinity in the nanomolar range. Concomitantly, ZBTB10 co-localizes with a subset of telomeres in ALT-positive U2OS cells and interacts with TRF2/RAP1 via the N-terminal region of TRF2. Our data establishes ZBTB10 as a novel variant repeat binding protein at ALT telomeres.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / genetics
  • Chromosomes / genetics
  • DNA-Binding Proteins / genetics
  • Genome / genetics
  • Humans
  • Protein Binding / genetics
  • Repetitive Sequences, Nucleic Acid / genetics
  • Repressor Proteins / genetics*
  • Telomere / genetics*
  • Telomere Homeostasis / genetics*
  • Telomere-Binding Proteins / genetics
  • Telomeric Repeat Binding Protein 2 / genetics*

Substances

  • DNA-Binding Proteins
  • Repressor Proteins
  • TERF2 protein, human
  • TERF2IP protein, human
  • Telomere-Binding Proteins
  • Telomeric Repeat Binding Protein 2
  • ZBTB10 protein, human