Published online 12 January 2005
Article |
GM-CSF promoter chromatin remodelling and gene transcription display distinct signal and transcription factor requirements
Discipline of Biochemistry, University of Tasmania Private Bag 58, Hobart 7001, Tasmania, Australia 1 Division of Immunology and Genetics, John Curtin School of Medical Research, Australian National University ACT, Australia 2 Division of Molecular Biosciences, John Curtin School of Medical Research, Australian National University ACT, Australia
*To whom correspondence should be addressed. Tel: +61 0 3 62262670; Fax: +61 03 62262703; Email: A.F.Holloway{at}utas.edu.au
Received December 9, 2004. Accepted December 13, 2004.
Granulocyte-macrophage colony stimulating factor (GM-CSF) plays a key role in myeloid cell function and is rapidly and transiently expressed in T cells in response to immune or inflammatory stimuli. Induction of GM-CSF gene expression is accompanied by changes in chromatin structure across the proximal promoter region of the gene. We show that the promoter remodelling and subsequent gene transcription occurs with distinct signal and transcription factor requirements. Activation of the protein kinase C (PKC) signalling pathway is sufficient to induce changes in chromatin structure across the promoter, but both the PKC and calcium signalling pathways are required for efficient gene transcription. Although NFAT transcription factors contribute to GM-CSF gene transcription, they are not required for promoter remodelling. However, the presence of the nuclear factor-
B transcription factor, c-Rel, in the nucleus is strongly correlated with and required for the events of chromatin remodelling.
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