ATRX proximal protein associations boast roles beyond histone deposition

PLoS Genet. 2021 Nov 15;17(11):e1009909. doi: 10.1371/journal.pgen.1009909. eCollection 2021 Nov.

Abstract

The ATRX ATP-dependent chromatin remodelling/helicase protein associates with the DAXX histone chaperone to deposit histone H3.3 over repetitive DNA regions. Because ATRX-protein interactions impart functions, such as histone deposition, we used proximity-dependent biotinylation (BioID) to identify proximal associations for ATRX. The proteomic screen captured known interactors, such as DAXX, NBS1, and PML, but also identified a range of new associating proteins. To gauge the scope of their roles, we examined three novel ATRX-associating proteins that likely differed in function, and for which little data were available. We found CCDC71 to associate with ATRX, but also HP1 and NAP1, suggesting a role in chromatin maintenance. Contrastingly, FAM207A associated with proteins involved in ribosome biosynthesis and localized to the nucleolus. ATRX proximal associations with the SLF2 DNA damage response factor help inhibit telomere exchanges. We further screened for the proteomic changes at telomeres when ATRX, SLF2, or both proteins were deleted. The loss caused important changes in the abundance of chromatin remodelling, DNA replication, and DNA repair factors at telomeres. Interestingly, several of these have previously been implicated in alternative lengthening of telomeres. Altogether, this study expands the repertoire of ATRX-associating proteins and functions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biotinylation / genetics
  • Cell Cycle Proteins / genetics
  • Cell Line
  • Chromatin / genetics
  • Chromobox Protein Homolog 5 / genetics
  • Co-Repressor Proteins / genetics*
  • DNA Damage / genetics
  • DNA Repair / genetics
  • DNA-Binding Proteins / genetics*
  • Histone Chaperones / genetics
  • Histones / genetics
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Molecular Chaperones / genetics
  • Nuclear Proteins / genetics*
  • Promyelocytic Leukemia Protein / genetics
  • Telomere / genetics
  • X-linked Nuclear Protein / genetics*
  • tRNA Methyltransferases

Substances

  • CCDC71 protein, human
  • Cell Cycle Proteins
  • Chromatin
  • Co-Repressor Proteins
  • DAXX protein, human
  • DNA-Binding Proteins
  • HP1-alpha protein, human
  • Histone Chaperones
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Molecular Chaperones
  • NBN protein, human
  • Nuclear Proteins
  • Promyelocytic Leukemia Protein
  • SLF2 protein, human
  • Chromobox Protein Homolog 5
  • PML protein, human
  • TRMO protein, human
  • tRNA Methyltransferases
  • ATRX protein, human
  • X-linked Nuclear Protein