TRF1 and TRF2 binding to telomeres is modulated by nucleosomal organization

Nucleic Acids Res. 2015 Jul 13;43(12):5824-37. doi: 10.1093/nar/gkv507. Epub 2015 May 20.

Abstract

The ends of eukaryotic chromosomes need to be protected from the activation of a DNA damage response that leads the cell to replicative senescence or apoptosis. In mammals, protection is accomplished by a six-factor complex named shelterin, which organizes the terminal TTAGGG repeats in a still ill-defined structure, the telomere. The stable interaction of shelterin with telomeres mainly depends on the binding of two of its components, TRF1 and TRF2, to double-stranded telomeric repeats. Tethering of TRF proteins to telomeres occurs in a chromatin environment characterized by a very compact nucleosomal organization. In this work we show that binding of TRF1 and TRF2 to telomeric sequences is modulated by the histone octamer. By means of in vitro models, we found that TRF2 binding is strongly hampered by the presence of telomeric nucleosomes, whereas TRF1 binds efficiently to telomeric DNA in a nucleosomal context and is able to remodel telomeric nucleosomal arrays. Our results indicate that the different behavior of TRF proteins partly depends on the interaction with histone tails of their divergent N-terminal domains. We propose that the interplay between the histone octamer and TRF proteins plays a role in the steps leading to telomere deprotection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • DNA / metabolism
  • Histones / metabolism
  • Nucleosomes / chemistry
  • Nucleosomes / metabolism*
  • Protein Binding
  • Protein Structure, Tertiary
  • Repetitive Sequences, Nucleic Acid
  • Telomere / chemistry
  • Telomere / metabolism*
  • Telomeric Repeat Binding Protein 1 / chemistry
  • Telomeric Repeat Binding Protein 1 / metabolism*
  • Telomeric Repeat Binding Protein 2 / chemistry
  • Telomeric Repeat Binding Protein 2 / metabolism*

Substances

  • Histones
  • Nucleosomes
  • Telomeric Repeat Binding Protein 1
  • Telomeric Repeat Binding Protein 2
  • DNA