Interaction of nucleolin with ribosomal RNA genes and its role in RNA polymerase I transcription

Nucleic Acids Res. 2012 Oct;40(19):9441-54. doi: 10.1093/nar/gks720. Epub 2012 Aug 2.

Abstract

Nucleolin is a multi-functional nucleolar protein that is required for ribosomal RNA gene (rRNA) transcription in vivo, but the mechanism by which nucleolin modulates RNA polymerase I (RNAPI) transcription is not well understood. Nucleolin depletion results in an increase in the heterochromatin mark H3K9me2 and a decrease in H4K12Ac and H3K4me3 euchromatin histone marks in rRNA genes. ChIP-seq experiments identified an enrichment of nucleolin in the ribosomal DNA (rDNA) coding and promoter region. Nucleolin is preferentially associated with unmethylated rRNA genes and its depletion leads to the accumulation of RNAPI at the beginning of the transcription unit and a decrease in UBF along the coding and promoter regions. Nucleolin is able to affect the binding of transcription termination factor-1 on the promoter-proximal terminator T0, thus inhibiting the recruitment of TIP5 and HDAC1 and the establishment of a repressive heterochromatin state. These results reveal the importance of nucleolin for the maintenance of the euchromatin state and transcription elongation of rDNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / metabolism
  • DNA, Ribosomal / chemistry
  • DNA, Ribosomal / metabolism
  • DNA-Binding Proteins / metabolism
  • Epigenesis, Genetic
  • Genes, rRNA*
  • HeLa Cells
  • Humans
  • Phosphoproteins / antagonists & inhibitors
  • Phosphoproteins / metabolism*
  • Phosphoproteins / physiology
  • RNA Polymerase I / metabolism*
  • RNA-Binding Proteins / antagonists & inhibitors
  • RNA-Binding Proteins / metabolism*
  • RNA-Binding Proteins / physiology
  • Repetitive Sequences, Nucleic Acid
  • Terminator Regions, Genetic
  • Transcription Factors
  • Transcription, Genetic*

Substances

  • Chromatin
  • DNA, Ribosomal
  • DNA-Binding Proteins
  • Phosphoproteins
  • RNA-Binding Proteins
  • TTF1 protein, human
  • Transcription Factors
  • nucleolin
  • RNA Polymerase I