Chromatin landscape dictates HSF binding to target DNA elements

PLoS Genet. 2010 Sep 9;6(9):e1001114. doi: 10.1371/journal.pgen.1001114.

Abstract

Sequence-specific transcription factors (TFs) are critical for specifying patterns and levels of gene expression, but target DNA elements are not sufficient to specify TF binding in vivo. In eukaryotes, the binding of a TF is in competition with a constellation of other proteins, including histones, which package DNA into nucleosomes. We used the ChIP-seq assay to examine the genome-wide distribution of Drosophila Heat Shock Factor (HSF), a TF whose binding activity is mediated by heat shock-induced trimerization. HSF binds to 464 sites after heat shock, the vast majority of which contain HSF Sequence-binding Elements (HSEs). HSF-bound sequence motifs represent only a small fraction of the total HSEs present in the genome. ModENCODE ChIP-chip datasets, generated during non-heat shock conditions, were used to show that inducibly bound HSE motifs are associated with histone acetylation, H3K4 trimethylation, RNA Polymerase II, and coactivators, compared to HSE motifs that remain HSF-free. Furthermore, directly changing the chromatin landscape, from an inactive to an active state, permits inducible HSF binding. There is a strong correlation of bound HSEs to active chromatin marks present prior to induced HSF binding, indicating that an HSE's residence in "active" chromatin is a primary determinant of whether HSF can bind following heat shock.

Publication types

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

MeSH terms

  • Animals
  • Base Sequence
  • Binding Sites
  • Chromatin / metabolism*
  • Chromatin Immunoprecipitation
  • Consensus Sequence / genetics
  • DNA / metabolism*
  • DNA-Binding Proteins / deficiency
  • DNA-Binding Proteins / metabolism*
  • Drosophila Proteins / deficiency
  • Drosophila Proteins / metabolism*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism*
  • Heat Shock Transcription Factors
  • Molecular Sequence Data
  • Promoter Regions, Genetic*
  • Protein Binding
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Transcription Factors / deficiency
  • Transcription Factors / metabolism*
  • Transcriptional Activation / genetics

Substances

  • Chromatin
  • DNA-Binding Proteins
  • Drosophila Proteins
  • Heat Shock Transcription Factors
  • Hsf protein, Drosophila
  • RNA, Messenger
  • Transcription Factors
  • DNA