Mot1, Ino80C, and NC2 Function Coordinately to Regulate Pervasive Transcription in Yeast and Mammals

Mol Cell. 2017 Aug 17;67(4):594-607.e4. doi: 10.1016/j.molcel.2017.06.029. Epub 2017 Jul 20.

Abstract

Pervasive transcription initiates from cryptic promoters and is observed in eukaryotes ranging from yeast to mammals. The Set2-Rpd3 regulatory system prevents cryptic promoter function within expressed genes. However, conserved systems that control pervasive transcription within intergenic regions have not been well established. Here we show that Mot1, Ino80 chromatin remodeling complex (Ino80C), and NC2 co-localize on chromatin and coordinately suppress pervasive transcription in S. cerevisiae and murine embryonic stem cells (mESCs). In yeast, all three proteins bind subtelomeric heterochromatin through a Sir3-stimulated mechanism and to euchromatin via a TBP-stimulated mechanism. In mESCs, the proteins bind to active and poised TBP-bound promoters along with promoters of polycomb-silenced genes apparently lacking TBP. Depletion of Mot1, Ino80C, or NC2 by anchor away in yeast or RNAi in mESCs leads to near-identical transcriptome phenotypes, with new subtelomeric transcription in yeast, and greatly increased pervasive transcription in both yeast and mESCs.

Keywords: Ino80; Mot1; NC2; Sir3; heterochromatin; pervasive transcription; polycomb; promoter; silencing.

MeSH terms

  • Adenosine Triphosphatases / genetics
  • Adenosine Triphosphatases / metabolism*
  • Binding Sites
  • Cell Line
  • Embryonic Stem Cells / enzymology*
  • Euchromatin / genetics
  • Euchromatin / metabolism
  • Gene Expression Regulation, Fungal
  • Gene Silencing
  • Genotype
  • Heterochromatin / genetics
  • Heterochromatin / metabolism
  • Phenotype
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism*
  • Promoter Regions, Genetic
  • Protein Binding
  • RNA Interference
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / genetics
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae / metabolism
  • TATA-Binding Protein Associated Factors / genetics
  • TATA-Binding Protein Associated Factors / metabolism*
  • TATA-Box Binding Protein / genetics
  • TATA-Box Binding Protein / metabolism
  • Transcription Factor TFIID
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription, Genetic*
  • Transfection

Substances

  • BTAF1 protein, mouse
  • BUR6 protein, S cerevisiae
  • Euchromatin
  • Heterochromatin
  • INO80 complex, S cerevisiae
  • Phosphoproteins
  • Repressor Proteins
  • SIR3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Silent Information Regulator Proteins, Saccharomyces cerevisiae
  • TATA-Binding Protein Associated Factors
  • TATA-Box Binding Protein
  • Transcription Factor TFIID
  • Transcription Factors
  • down-regulator of transcription 1
  • Adenosine Triphosphatases
  • MOT1 protein, S cerevisiae
  • INO80 protein, mouse