Intrinsic promoter nucleosome stability/dynamics variations support a novel targeting mechanism

Biochemistry. 2009 May 26;48(20):4217-9. doi: 10.1021/bi900476t.

Abstract

Genomic processes like transcription initiation typically involve the alteration of nucleosome structure, to expose DNA elements for regulatory factor binding. Nucleosome altering/modifying complexes have been identified, but precisely how these complexes find their specific targets remains unclear. We have shown that nucleosomes can exhibit significant DNA sequence-dependent stability and dynamics variations and have suggested that these inherent variations could facilitate nucleosome recognition and thus aid in specific targeting. Here, we confirm an important prediction of the model, namely, that stability and DNA dynamics features can correlate with the transcriptional involvement of specific promoter nucleosomes. A transcriptionally inert Mouse Mammary Tumor Virus promoter-region nucleosome (MMTV-D) has greater inherent stability than and reduced dynamics compared to a nearby nucleosome (MMTV-B) that is the initial target of transcription activation-associated processes on this promoter. MMTV-D stability could help direct activation-associated events to the less stable and more dynamic target, MMTV-B.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • DNA / chemistry
  • DNA / genetics
  • Fluorescence Resonance Energy Transfer / methods
  • Humans
  • Kinetics
  • Mammary Tumor Virus, Mouse / genetics
  • Models, Genetic*
  • Nucleosomes / metabolism*
  • Promoter Regions, Genetic*
  • Receptors, Glucocorticoid / chemistry
  • Regulatory Sequences, Nucleic Acid
  • Transcription, Genetic

Substances

  • Nucleosomes
  • Receptors, Glucocorticoid
  • DNA