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| A nucleosomal function for I kappa B kinase-alpha in NF-kappa B-dependent gene expression |
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| Author(s): Anest V, Hanson JL, Cogswell PC, Steinbrecher KA, Strahl BD, Baldwin AS |
| Source: NATURE Volume: 423 Issue: 6940 Pages: 659-663 Published: JUN 5 2003 |
| Times Cited: 241 References: 22 |
| Abstract: NF-kappaB is a principal transcriptional regulator of diverse cytokine-mediated processes and is tightly controlled by the IkappaB kinase complex (IKK-alpha/beta/gamma). IKK-beta and IKK-gamma are critical for cytokine-induced NF-kappaB function, whereas IKK-alpha is thought to be involved in other regulatory pathways(1-4). However, recent data suggest a role for IKK-alpha in NF-kappaB-dependent gene expression in response to cytokine treatment(1,5-7). Here we demonstrate nuclear accumulation of IKK-alpha after cytokine exposure, suggesting a nuclear function for this protein. Consistent with this, chromatin immunoprecipitation (ChIP) assays reveal that IKK-alpha was recruited to the promoter regions of NF-kappaB-regulated genes on stimulation with tumour-necrosis factor-alpha. Notably, NF-kappaB-regulated gene expression is suppressed by the loss of IKK-alpha 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-alpha can directly phosphorylate histone H3 in vitro, suggesting a new substrate for this kinase. We propose that IKK-alpha is an essential regulator of NF-kappaB-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-kappaB-regulated gene expression. |
| Document Type: Article |
| Language: English |
| Reprint Address: Baldwin, AS (reprint author), Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA |
Addresses:
1. Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
2. Univ N Carolina, Curriculum Genet & Mol Biol, Chapel Hill, NC 27599 USA
3. Univ N Carolina, Dept Biochem & Biophys, Chapel Hill, NC 27599 USA
4. Univ N Carolina, Dept Biol, Chapel Hill, NC 27599 USA |
| Publisher: NATURE PUBLISHING GROUP, MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND |
| Subject Category: Multidisciplinary Sciences |
| IDS Number: 686BT |
| ISSN: 0028-0836 |
| DOI: 10.1038/nature01648 |
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