Histone dynamics on the interleukin-2 gene in response to T-cell activation.
Several models have been proposed for the mechanism of chromatin remodelling across the promoters of inducible genes in mammalian cells. The most commonly held model is one of cooccupation where histone proteins are modified by acetylation or phosphorylation and nucleosomes are remodelled, allowing the assembly of transcription factor complexes. Using chromatin immunoprecipitation, we observed an apparent decrease of histone acetylation and phosphorylation signals at the proximal promoter region of the inducible interleukin-2 and granulocyte-macrophage colony-stimulating factor genes in response to T-cell activation. We showed that this apparent decrease was due to a loss of histone H3 and H4 proteins corresponding to a decrease in nucleosome occupation of the promoter. This histone loss is reversible; it is dependent on the continual presence of appropriate activating signals and transcription factors and is not dependent on the acetylation status of the histone proteins. These data show for the first time that histone proteins are lost from a mammalian promoter upon activation of transcription and support a model of activation-dependent disassembly and reassembly of nucleosomes.
Chen
Xinxin
X
Division of Molecular Bioscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia.
Wang
Jun
J
Woltring
Donna
D
Gerondakis
Steve
S
Shannon
M Frances
MF
D000107:Acetylation; D000818:Animals; D002478:Cells, Cultured; D042002:Chromatin Assembly and Disassembly / Q000502:physiology*; D047369:Chromatin Immunoprecipitation; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000235:genetics; D006657:Histones / Q000378:metabolism*; D007376:Interleukin-2 / Q000235:genetics*; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D009707:Nucleosomes / Q000378:metabolism; D010766:Phosphorylation; D011401:Promoter Regions, Genetic / Q000502:physiology*; D013601:T-Lymphocytes / Q000502:physiology*; D014157:Transcription Factors; D015533:Transcriptional Activation
D006657:Histones; D007376:Interleukin-2; D009707:Nucleosomes; D014157:Transcription Factors; D016178:Granulocyte-Macrophage Colony-Stimulating Factor