Author
Listed:
- Vasiliki Anest
(Lineberger Comprehensive Cancer Center)
- Julie L. Hanson
(Lineberger Comprehensive Cancer Center
Curriculum in Genetics and Molecular Biology)
- Patricia C. Cogswell
(Lineberger Comprehensive Cancer Center)
- Kris A. Steinbrecher
(Lineberger Comprehensive Cancer Center)
- Brian D. Strahl
(Lineberger Comprehensive Cancer Center
Curriculum in Genetics and Molecular Biology
Department of Biochemistry and Biophysics)
- Albert S. Baldwin
(Lineberger Comprehensive Cancer Center
Curriculum in Genetics and Molecular Biology
University of North Carolina)
Abstract
NF-κB is a principal transcriptional regulator of diverse cytokine-mediated processes and is tightly controlled by the IκB kinase complex (IKK-α/β/γ). IKK-β and IKK-γ are critical for cytokine-induced NF-κB function, whereas IKK-α is thought to be involved in other regulatory pathways1,2,3,4. However, recent data suggest a role for IKK-α in NF-κB-dependent gene expression in response to cytokine treatment1,5,6,7. Here we demonstrate nuclear accumulation of IKK-α after cytokine exposure, suggesting a nuclear function for this protein. Consistent with this, chromatin immunoprecipitation (ChIP) assays reveal that IKK-α was recruited to the promoter regions of NF-κB-regulated genes on stimulation with tumour-necrosis factor-α. Notably, NF-κB-regulated gene expression is suppressed by the loss of IKK-α and this correlates with a complete loss of gene-specific phosphorylation of histone H3 on serine 10, a modification previously associated with positive gene expression. Furthermore, we show that IKK-α can directly phosphorylate histone H3 in vitro, suggesting a new substrate for this kinase. We propose that IKK-α is an essential regulator of NF-κB-dependent gene expression through control of promoter-associated histone phosphorylation after cytokine exposure. These findings provide additional insight into the role of the IKK complex in NF-κB-regulated gene expression.
Suggested Citation
Vasiliki Anest & Julie L. Hanson & Patricia C. Cogswell & Kris A. Steinbrecher & Brian D. Strahl & Albert S. Baldwin, 2003.
"A nucleosomal function for IκB kinase-α in NF-κB-dependent gene expression,"
Nature, Nature, vol. 423(6940), pages 659-663, June.
Handle:
RePEc:nat:nature:v:423:y:2003:i:6940:d:10.1038_nature01648
DOI: 10.1038/nature01648
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