Inhibition of DNA methylation alters chromatin organization, nuclear positioning and activity of 45S rDNA loci in cycling cells of Q. robur

PLoS One. 2014 Aug 5;9(8):e103954. doi: 10.1371/journal.pone.0103954. eCollection 2014.

Abstract

Around 2200 copies of genes encoding ribosomal RNA (rRNA) in pedunculate oak, Quercus robur, are organized into two rDNA loci, the major (NOR-1) and the minor (NOR-2) locus. We present the first cytogenetic evidence indicating that the NOR-1 represents the active nucleolar organizer responsible for rRNA synthesis, while the NOR-2 probably stays transcriptionally silent and does not participate in the formation of the nucleolus in Q. robur, which is a situation resembling the well-known phenomenon of nucleolar dominance. rDNA chromatin topology analyses in cycling root tip cells by light and electron microscopy revealed the minor locus to be highly condensed and located away from the nucleolus, while the major locus was consistently associated with the nucleolus and often exhibited different levels of condensation. In addition, silver precipitation was confined exclusively to the NOR-1 locus. Also, NOR-2 was highly methylated at cytosines and rDNA chromatin was marked with histone modifications characteristic for repressive state. After treatment of the root cells with the methylation inhibitor 5-aza-2'-deoxycytidine, we observed an increase in the total level of rRNA transcripts and a decrease in DNA methylation level at the NOR-2 locus. Also, NOR-2 sites relocalized with respect to the nuclear periphery/nucleolus, however, the relocation did not affect the contribution of this locus to nucleolar formation, nor did it affect rDNA chromatin decondensation, strongly suggesting that NOR-2 has lost the function of rRNA synthesis and nucleolar organization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Cycle / genetics*
  • Cell Nucleus / metabolism*
  • Chromatin / chemistry
  • Chromatin / metabolism*
  • DNA Methylation*
  • DNA, Ribosomal / genetics*
  • Down-Regulation / genetics
  • Genes, rRNA
  • Genetic Loci
  • In Situ Hybridization, Fluorescence
  • Nucleolus Organizer Region / genetics
  • Nucleolus Organizer Region / metabolism
  • Quercus / genetics*

Substances

  • Chromatin
  • DNA, Ribosomal

Grants and funding

The work was supported by the Croatian Ministry of Science, Education and Sport Grant (grant no. 119-1191196-1224), AUF PCSI Grant, and FP7 RegPot Integra-Life grant (grant no. 315997). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.