Human PIH1 associates with histone H4 to mediate the glucose-dependent enhancement of pre-rRNA synthesis

J Mol Cell Biol. 2012 Aug;4(4):231-41. doi: 10.1093/jmcb/mjs003. Epub 2012 Feb 24.

Abstract

Ribosome biogenesis is critical in the growth of eukaryotic cells, in which the synthesis of precursor ribosomal RNA is the first and rate-limiting step. Here, we show that human PIH1 domain-containing protein 1 (PIH1) interacts directly with histone H4 and recruits the Brg1-SWI/SNF complex via SNF5 to human rRNA genes. This process is likely involved in PIH1-dependent DNase I-hypersensitive chromatin remodeling at the core promoter of the rRNA genes. PIH1 mediates the occupancy of not only the Brg1 complex but also the Pol I complex at the core promoter and enhances transcription initiation of rRNA genes. Additionally, the interaction between PIH1 and H4K16 expels TIP5, a component of the silencing nucleolar remodeling complex (NoRC), from the core region, suggesting that PIH1 is involved in the derepression of NoRC-silenced rRNA genes. These data indicate that PIH1 is a positive regulator of human rRNA genes and is of great importance for the recovery of human cells from nutrient starvation and the transition to glucose-induced exponential growth in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis Regulatory Proteins / metabolism*
  • Chromatin Assembly and Disassembly / drug effects
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Deoxyribonuclease I / metabolism
  • Gene Expression Regulation / drug effects
  • Genes, rRNA / genetics
  • Glucose / pharmacology*
  • HEK293 Cells
  • Histones / metabolism*
  • Humans
  • Models, Biological
  • Promoter Regions, Genetic / genetics
  • Protein Binding / drug effects
  • RNA Precursors / biosynthesis*
  • SMARCB1 Protein
  • Transcription Factors

Substances

  • Apoptosis Regulatory Proteins
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • Histones
  • PIH1D1 protein, human
  • RNA Precursors
  • SMARCB1 Protein
  • SMARCB1 protein, human
  • Transcription Factors
  • Deoxyribonuclease I
  • Glucose