A nucleosomal function for iκb kinase-α in nf-κb-dependent gene expression

Vasiliki Anest, Julie L. Hanson, Patricia C. Cogswell, Kris A. Steinbrecher, Brian D. Strahl, Albert S. Baldwin

Research output: Contribution to journalArticle

425 Citations (Scopus)

Abstract

NF-κB is a principal transcriptional regulator of diverse cyto-kine-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 pathways. However, recent data suggest a role for IKK-α in NF-κB-dependent gene expression in response to cytokine treatment. 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.

Original languageEnglish (US)
Pages (from-to)659-663
Number of pages5
JournalNature
Volume423
Issue number6940
DOIs
StatePublished - Jun 5 2003

Fingerprint

Phosphotransferases
Gene Expression
Histones
Cytokines
Phosphorylation
Chromatin Immunoprecipitation
Nuclear Proteins
Genetic Promoter Regions
Serine
Genes
Tumor Necrosis Factor-alpha

Cite this

Anest, V., Hanson, J. L., Cogswell, P. C., Steinbrecher, K. A., Strahl, B. D., & Baldwin, A. S. (2003). A nucleosomal function for iκb kinase-α in nf-κb-dependent gene expression. Nature, 423(6940), 659-663. https://doi.org/10.1038/nature01648

A nucleosomal function for iκb kinase-α in nf-κb-dependent gene expression. / Anest, Vasiliki; Hanson, Julie L.; Cogswell, Patricia C.; Steinbrecher, Kris A.; Strahl, Brian D.; Baldwin, Albert S.

In: Nature, Vol. 423, No. 6940, 05.06.2003, p. 659-663.

Research output: Contribution to journalArticle

Anest, V, Hanson, JL, Cogswell, PC, Steinbrecher, KA, Strahl, BD & Baldwin, AS 2003, 'A nucleosomal function for iκb kinase-α in nf-κb-dependent gene expression', Nature, vol. 423, no. 6940, pp. 659-663. https://doi.org/10.1038/nature01648
Anest V, Hanson JL, Cogswell PC, Steinbrecher KA, Strahl BD, Baldwin AS. A nucleosomal function for iκb kinase-α in nf-κb-dependent gene expression. Nature. 2003 Jun 5;423(6940):659-663. https://doi.org/10.1038/nature01648
Anest, Vasiliki ; Hanson, Julie L. ; Cogswell, Patricia C. ; Steinbrecher, Kris A. ; Strahl, Brian D. ; Baldwin, Albert S. / A nucleosomal function for iκb kinase-α in nf-κb-dependent gene expression. In: Nature. 2003 ; Vol. 423, No. 6940. pp. 659-663.
@article{24b5af99affd46c6a3e1114eb2ced005,
title = "A nucleosomal function for iκb kinase-α in nf-κb-dependent gene expression",
abstract = "NF-κB is a principal transcriptional regulator of diverse cyto-kine-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 pathways. However, recent data suggest a role for IKK-α in NF-κB-dependent gene expression in response to cytokine treatment. 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.",
author = "Vasiliki Anest and Hanson, {Julie L.} and Cogswell, {Patricia C.} and Steinbrecher, {Kris A.} and Strahl, {Brian D.} and Baldwin, {Albert S.}",
year = "2003",
month = "6",
day = "5",
doi = "10.1038/nature01648",
language = "English (US)",
volume = "423",
pages = "659--663",
journal = "Nature",
issn = "0028-0836",
publisher = "Nature Publishing Group",
number = "6940",

}

TY - JOUR

T1 - A nucleosomal function for iκb kinase-α in nf-κb-dependent gene expression

AU - Anest, Vasiliki

AU - Hanson, Julie L.

AU - Cogswell, Patricia C.

AU - Steinbrecher, Kris A.

AU - Strahl, Brian D.

AU - Baldwin, Albert S.

PY - 2003/6/5

Y1 - 2003/6/5

N2 - NF-κB is a principal transcriptional regulator of diverse cyto-kine-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 pathways. However, recent data suggest a role for IKK-α in NF-κB-dependent gene expression in response to cytokine treatment. 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.

AB - NF-κB is a principal transcriptional regulator of diverse cyto-kine-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 pathways. However, recent data suggest a role for IKK-α in NF-κB-dependent gene expression in response to cytokine treatment. 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.

UR - http://www.scopus.com/inward/record.url?scp=0037497184&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037497184&partnerID=8YFLogxK

U2 - 10.1038/nature01648

DO - 10.1038/nature01648

M3 - Article

VL - 423

SP - 659

EP - 663

JO - Nature

JF - Nature

SN - 0028-0836

IS - 6940

ER -