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Hyperactivated NF-κB and AP-1 transcription factors promote highly accessible chromatin and constitutive transcription across the interleukin-6 gene promoter in metastatic breast cancer cells

Matladi N Ndlovu, Carine Van Lint, Karlien Van Wesemael UGent, Pieter Callebert UGent, Dany Chalbos, Guy Haegeman UGent and Wim Vanden Berghe UGent (2009) MOLECULAR AND CELLULAR BIOLOGY. 29(20). p.5488-5504
abstract
Interleukin-6 (IL-6), involved in cancer-related inflammation, acts as an autocrine and paracrine growth factor, which promotes angiogenesis, metastasis, and subversion of immunity, and changes the response to hormones and to chemotherapeutics. We explored transcription mechanisms involved in differential IL-6 gene expression in breast cancer cells with different metastatic properties. In weakly metastatic MCF7 cells, histone H3 K9 methylation, HP1 binding, and weak recruitment of AP-1 Fra-1/c-Jun, NF-kappa B p65 transcription factors, and coactivators is indicative of low chromatin accessibility and gene transcription at the IL-6 gene promoter. In highly metastatic MDA-MB231 cells, strong DNase, MNase, and restriction enzyme accessibility, as well potent constitutive transcription of the IL-6 gene promoter, coincide with increased H3 S10 K14 phosphoacetylation and promoter enrichment of AP-1 Fra-1/c-Jun and NF-kappa B p65 transcription factors and MSK1, CBP/p300, Brg1, and Ezh2 cofactors. Complementation, silencing, and kinase inhibitor experiments further demonstrate involvement of AP-1 Fra-1/c-Jun and NF-kappa B p65/RelB members, but not of the alpha estrogen receptor in promoting chromatin accessibility and transcription across the IL-6 gene promoter in metastatic breast cancer cells. Finally, the natural withanolide Withaferin A was found to repress IL-6 gene transcription in metastatic breast cancer cells upon dual inhibition of NF-kappa B and AP-1 Fra-1 transcription factors and silencing of IL-6 promoter chromatin accessibility.
Please use this url to cite or link to this publication:
author
organization
alternative title
Hyperactivated NF-kappa B and AP-1 transcription factors promote highly accessible chromatin and constitutive transcription across the interleukin-6 gene promoter in metastatic breast cancer cells
year
type
journalArticle (original)
publication status
published
subject
keyword
HISTONE H3, PROSTATE-CANCER, GM-CSF PROMOTER, IMMUNODEFICIENCY-VIRUS TYPE-1, EPIGENETIC MECHANISMS, MONOALLELIC EXPRESSION, WITHAFERIN-A, HUMAN GENOME, INVASIVE PHENOTYPE, NATURAL-PRODUCTS
journal title
MOLECULAR AND CELLULAR BIOLOGY
Mol. Cell. Biol.
volume
29
issue
20
pages
5488 - 5504
Web of Science type
Article
Web of Science id
000270271100009
JCR category
BIOCHEMISTRY & MOLECULAR BIOLOGY
JCR impact factor
6.057 (2009)
JCR rank
40/281 (2009)
JCR quartile
1 (2009)
ISSN
0270-7306
DOI
10.1128/MCB.01657-08
language
English
UGent publication?
yes
classification
A1
copyright statement
I have transferred the copyright for this publication to the publisher
id
970282
handle
http://hdl.handle.net/1854/LU-970282
date created
2010-06-06 11:41:53
date last changed
2010-06-22 12:21:18
@article{970282,
  abstract     = {Interleukin-6 (IL-6), involved in cancer-related inflammation, acts as an autocrine and paracrine growth factor, which promotes angiogenesis, metastasis, and subversion of immunity, and changes the response to hormones and to chemotherapeutics. We explored transcription mechanisms involved in differential IL-6 gene expression in breast cancer cells with different metastatic properties. In weakly metastatic MCF7 cells, histone H3 K9 methylation, HP1 binding, and weak recruitment of AP-1 Fra-1/c-Jun, NF-kappa B p65 transcription factors, and coactivators is indicative of low chromatin accessibility and gene transcription at the IL-6 gene promoter. In highly metastatic MDA-MB231 cells, strong DNase, MNase, and restriction enzyme accessibility, as well potent constitutive transcription of the IL-6 gene promoter, coincide with increased H3 S10 K14 phosphoacetylation and promoter enrichment of AP-1 Fra-1/c-Jun and NF-kappa B p65 transcription factors and MSK1, CBP/p300, Brg1, and Ezh2 cofactors. Complementation, silencing, and kinase inhibitor experiments further demonstrate involvement of AP-1 Fra-1/c-Jun and NF-kappa B p65/RelB members, but not of the alpha estrogen receptor in promoting chromatin accessibility and transcription across the IL-6 gene promoter in metastatic breast cancer cells. Finally, the natural withanolide Withaferin A was found to repress IL-6 gene transcription in metastatic breast cancer cells upon dual inhibition of NF-kappa B and AP-1 Fra-1 transcription factors and silencing of IL-6 promoter chromatin accessibility.},
  author       = {Ndlovu, Matladi N and Van Lint, Carine and Van Wesemael, Karlien and Callebert, Pieter and Chalbos, Dany and Haegeman, Guy and Vanden Berghe, Wim},
  issn         = {0270-7306},
  journal      = {MOLECULAR AND CELLULAR BIOLOGY},
  keyword      = {HISTONE H3,PROSTATE-CANCER,GM-CSF PROMOTER,IMMUNODEFICIENCY-VIRUS TYPE-1,EPIGENETIC MECHANISMS,MONOALLELIC EXPRESSION,WITHAFERIN-A,HUMAN GENOME,INVASIVE PHENOTYPE,NATURAL-PRODUCTS},
  language     = {eng},
  number       = {20},
  pages        = {5488--5504},
  title        = {Hyperactivated NF-\ensuremath{\kappa}B and AP-1 transcription factors promote highly accessible chromatin and constitutive transcription across the interleukin-6 gene promoter in metastatic breast cancer cells},
  url          = {http://dx.doi.org/10.1128/MCB.01657-08},
  volume       = {29},
  year         = {2009},
}

Chicago
Ndlovu, Matladi N, Carine Van Lint, Karlien Van Wesemael, Pieter Callebert, Dany Chalbos, Guy Haegeman, and Wim Vanden Berghe. 2009. “Hyperactivated NF-κB and AP-1 Transcription Factors Promote Highly Accessible Chromatin and Constitutive Transcription Across the Interleukin-6 Gene Promoter in Metastatic Breast Cancer Cells.” Molecular and Cellular Biology 29 (20): 5488–5504.
APA
Ndlovu, M. N., Van Lint, C., Van Wesemael, K., Callebert, P., Chalbos, D., Haegeman, G., & Vanden Berghe, W. (2009). Hyperactivated NF-κB and AP-1 transcription factors promote highly accessible chromatin and constitutive transcription across the interleukin-6 gene promoter in metastatic breast cancer cells. MOLECULAR AND CELLULAR BIOLOGY, 29(20), 5488–5504.
Vancouver
1.
Ndlovu MN, Van Lint C, Van Wesemael K, Callebert P, Chalbos D, Haegeman G, et al. Hyperactivated NF-κB and AP-1 transcription factors promote highly accessible chromatin and constitutive transcription across the interleukin-6 gene promoter in metastatic breast cancer cells. MOLECULAR AND CELLULAR BIOLOGY. 2009;29(20):5488–504.
MLA
Ndlovu, Matladi N, Carine Van Lint, Karlien Van Wesemael, et al. “Hyperactivated NF-κB and AP-1 Transcription Factors Promote Highly Accessible Chromatin and Constitutive Transcription Across the Interleukin-6 Gene Promoter in Metastatic Breast Cancer Cells.” MOLECULAR AND CELLULAR BIOLOGY 29.20 (2009): 5488–5504. Print.