A unifying model for the selective regulation of inducible transcription by CpG islands and nucleosome remodeling.
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.
Ramirez-Carrozzi
Vladimir R
VR
Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA.
Braas
Daniel
D
Bhatt
Dev M
DM
Cheng
Christine S
CS
Hong
Christine
C
Doty
Kevin R
KR
Black
Joshua C
JC
Hoffmann
Alexander
A
Carey
Michael
M
Smale
Stephen T
ST
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D018899:CpG Islands; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D002868:Chromosomal Proteins, Non-Histone; D050838:Interferon Regulatory Factor-3; D008070:Lipopolysaccharides; D009707:Nucleosomes; C445179:SWI-SNF-B chromatin-remodeling complex; D014157:Transcription Factors