Transcriptional activation of yeast genes disrupts intragenic nucleosome phasing

Nucleic Acids Res. 2012 Nov;40(21):10753-64. doi: 10.1093/nar/gks870. Epub 2012 Sep 24.

Abstract

Nucleosomes often undergo extensive rearrangement when genes are activated for transcription. We have shown previously, using paired-end sequencing of yeast nucleosomes, that major changes in chromatin structure occur when genes are activated by 3-aminotriazole (3AT), an inducer of the transcriptional activator Gcn4. Here, we provide a global analysis of these data. At the genomic level, nucleosomes are regularly phased relative to the transcription start site. However, for a subset of 234 strongly induced genes, this phasing is much more irregular after induction, consistent with the loss of some nucleosomes and the re-positioning of the remaining nucleosomes. To address the nature of this rearrangement, we developed the inter-nucleosome distance auto-correlation (DAC) function. At long range, DAC analysis indicates that nucleosomes have an average spacing of 162 bp, consistent with the reported repeat length. At short range, DAC reveals a 10.25-bp periodicity, implying that nucleosomes in overlapping positions are rotationally related. DAC analysis of the 3AT-induced genes suggests that transcription activation coincides with rearrangement of nucleosomes into irregular arrays with longer spacing. Sequence analysis of the +1 nucleosomes belonging to the 45 most strongly activated genes reveals a distinctive periodic oscillation in the A/T-dinucleotide occurrence that is present throughout the nucleosome and extends into the linker. This unusual pattern suggests that the +1 nucleosomes might be prone to sliding, thereby facilitating transcription.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Amitriptyline / pharmacology
  • Base Sequence
  • DNA / chemistry
  • Deoxyribonucleases
  • Gene Expression Regulation, Fungal*
  • Methyltransferases / genetics
  • Nucleosomes / chemistry*
  • Nucleosomes / drug effects
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / genetics
  • Transcriptional Activation*

Substances

  • Nucleosomes
  • Saccharomyces cerevisiae Proteins
  • Amitriptyline
  • DNA
  • MRM1 protein, S cerevisiae
  • Methyltransferases
  • Deoxyribonucleases