Evidence that Spt2/Sin1, an HMG-like factor, plays roles in transcription elongation, chromatin structure, and genome stability in Saccharomyces cerevisiae

Mol Cell Biol. 2006 Feb;26(4):1496-509. doi: 10.1128/MCB.26.4.1496-1509.2006.

Abstract

Spt2/Sin1 is a DNA binding protein with HMG-like domains that has been suggested to play a role in chromatin-mediated transcription in Saccharomyces cerevisiae. Previous studies have suggested models in which Spt2 plays an inhibitory role in the initiation of transcription of certain genes. In this work, we have taken several approaches to study Spt2 in greater detail. Our results have identified previously unknown genetic interactions between spt2Delta and mutations in genes encoding transcription elongation factors, including members of the PAF and HIR/HPC complexes. In addition, genome-wide and gene-specific chromatin immunoprecipitation analyses suggest that Spt2 is primarily associated with coding regions in a transcription-dependent fashion. Furthermore, our results show that Spt2, like other elongation factors, is required for the repression of transcription from a cryptic promoter within a coding region and that Spt2 is also required for repression of recombination within transcribed regions. Finally, we provide evidence that Spt2 plays a role in regulating the levels of histone H3 over transcribed regions. Taken together, our results suggest a direct link for Spt2 with transcription elongation, chromatin dynamics, and genome stability.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatin / genetics
  • Chromatin / metabolism
  • Chromosomal Proteins, Non-Histone / genetics*
  • Chromosomal Proteins, Non-Histone / metabolism*
  • DNA-Binding Proteins / genetics*
  • DNA-Binding Proteins / metabolism*
  • Genes, Fungal
  • Genomic Instability
  • Histone Chaperones
  • Histones / metabolism
  • Multiprotein Complexes
  • Mutation
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Recombination, Genetic
  • Repressor Proteins / genetics
  • Repressor Proteins / metabolism
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics*
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Transcription, Genetic
  • Transcriptional Elongation Factors / genetics
  • Transcriptional Elongation Factors / metabolism

Substances

  • Chromatin
  • Chromosomal Proteins, Non-Histone
  • DNA-Binding Proteins
  • HIR1 protein, S cerevisiae
  • HIR2 protein, S cerevisiae
  • Histone Chaperones
  • Histones
  • Multiprotein Complexes
  • Nuclear Proteins
  • Repressor Proteins
  • SPT6 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Transcriptional Elongation Factors
  • SPT2 protein, S cerevisiae