A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling

Cell. 2009 Jul 10;138(1):114-28. doi: 10.1016/j.cell.2009.04.020.


We describe a broad mechanistic framework for the transcriptional induction of mammalian primary response genes by Toll-like receptors and other stimuli. One major class of primary response genes is characterized by CpG-island promoters, which facilitate promiscuous induction from constitutively active chromatin without a requirement for SWI/SNF nucleosome remodeling complexes. The low nucleosome occupancy at promoters in this class can be attributed to the assembly of CpG islands into unstable nucleosomes, which may lead to SWI/SNF independence. Another major class consists of non-CpG-island promoters that assemble into stable nucleosomes, resulting in SWI/SNF dependence and a requirement for transcription factors that promote selective nucleosome remodeling. Some stimuli, including serum and tumor necrosis factor-alpha, exhibit a strong bias toward activation of SWI/SNF-independent CpG-island genes. In contrast, interferon-beta is strongly biased toward SWI/SNF-dependent non-CpG-island genes. By activating a diverse set of transcription factors, Toll-like receptors induce both classes and others for an optimal response to microbial pathogens.

Publication types

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

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / metabolism
  • Chromatin Assembly and Disassembly*
  • Chromosomal Proteins, Non-Histone / metabolism
  • CpG Islands*
  • Humans
  • Interferon Regulatory Factor-3 / metabolism
  • Lipopolysaccharides / immunology
  • Mice
  • Nucleosomes / metabolism
  • Promoter Regions, Genetic
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Transcriptional Activation*


  • Chromosomal Proteins, Non-Histone
  • Interferon Regulatory Factor-3
  • Lipopolysaccharides
  • Nucleosomes
  • SWI-SNF-B chromatin-remodeling complex
  • Transcription Factors