Reptin and Pontin oligomerization and activity are modulated through histone H3 N-terminal tail interaction

J Biol Chem. 2014 Dec 5;289(49):33999-4012. doi: 10.1074/jbc.M114.576785. Epub 2014 Oct 21.

Abstract

Pontin/RUVBL1 and Reptin/RUVBL2 are DNA-dependent ATPases involved in numerous cellular processes and are essential components of chromatin remodeling complexes and transcription factor assemblies. However, their existence as monomeric and oligomeric forms with differential activity in vivo reflects their versatility. Using a biochemical approach, we have studied the role of the nucleosome core particle and histone N-terminal tail modifications in the assembly and enzymatic activities of Reptin/Pontin. We demonstrate that purified Reptin and Pontin form stable complexes with nucleosomes. The ATPase activity of Reptin/Pontin is modulated by acetylation and methylation of the histone H3 N terminus. In vivo, association of Reptin with the progesterone receptor gene promoter is concomitant with changes in H3 marks of the surrounding nucleosomes. Furthermore, the presence of H3 tail peptides regulates the monomer-oligomer transition of Reptin/Pontin. Proteins that are pulled down by monomeric Reptin/Pontin differ from those that can bind to hexamers. We propose that changes in the oligomeric status of Reptin/Pontin create a platform that brings specific cofactors close to gene promoters and loads regulatory factors to establish an active state of chromatin.

Keywords: ATPase; Chromatin Remodeling; Histone Modification; Pontin/RUVBL1; Protein Conformation; Protein/DNA Interaction; Reptin/RUVBL2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATPases Associated with Diverse Cellular Activities
  • Amino Acid Sequence
  • Binding Sites
  • Carrier Proteins / chemistry
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell-Free System / chemistry
  • Cell-Free System / metabolism
  • DNA / chemistry
  • DNA / metabolism*
  • DNA Helicases / chemistry
  • DNA Helicases / genetics
  • DNA Helicases / metabolism*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Gene Expression
  • Histones / chemistry
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Molecular Sequence Data
  • Nucleosomes / chemistry
  • Nucleosomes / metabolism*
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Tertiary
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism

Substances

  • Carrier Proteins
  • Histones
  • Nucleosomes
  • Recombinant Proteins
  • DNA
  • ATPases Associated with Diverse Cellular Activities
  • DNA Helicases
  • RUVBL1 protein, human
  • RUVBL2 protein, human