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NF-κB- and AP-1-mediated DNA looping regulates osteopontin transcription in endotoxin-stimulated murine macrophages.

Publication ,  Journal Article
Zhao, W; Wang, L; Zhang, M; Wang, P; Zhang, L; Yuan, C; Qi, J; Qiao, Y; Kuo, PC; Gao, C
Published in: J Immunol
March 1, 2011

Osteopontin (OPN) is expressed by various immune cells and modulates both innate and adaptive immune responses. However, the molecular mechanisms that control opn gene expression, especially at the chromatin level, remain largely unknown. We have previously demonstrated many specific cis- and trans-regulatory elements that determine the extent of endotoxin (LPS)-mediated induction of OPN synthesis in murine macrophages. In the present study, we confirm that NF-κB also plays an important role in the setting of LPS-stimulated OPN expression through binding to a distal regulatory element. Importantly, we demonstrate that LPS stimulates chromosomal loops in the OPN promoter between NF-κB binding site and AP-1 binding site using chromosome conformation capture technology. The crucial role of NF-κB and AP-1 in LPS-stimulated DNA looping was confirmed, as small interfering RNA knock-down of NF-κB p65 and AP-1 c-Jun exhibited decreased levels of DNA looping. Furthermore, we demonstrate that p300 can form a complex with NF-κB and AP-1 and is involved in DNA looping and LPS-induced OPN expression. Therefore, we have identified an essential mechanism to remodel the local chromatin structures and spatial conformations to regulate LPS-induced OPN expression.

Duke Scholars

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Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 1, 2011

Volume

186

Issue

5

Start / End Page

3173 / 3179

Location

United States

Related Subject Headings

  • p300-CBP Transcription Factors
  • Transcription, Genetic
  • Transcription Factor RelA
  • Transcription Factor AP-1
  • RNA, Small Interfering
  • Proto-Oncogene Proteins c-jun
  • Protein Binding
  • Osteopontin
  • Nucleic Acid Conformation
  • NF-kappa B
 

Citation

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Zhao, W., Wang, L., Zhang, M., Wang, P., Zhang, L., Yuan, C., … Gao, C. (2011). NF-κB- and AP-1-mediated DNA looping regulates osteopontin transcription in endotoxin-stimulated murine macrophages. J Immunol, 186(5), 3173–3179. https://doi.org/10.4049/jimmunol.1003626
Zhao, Wei, Lijuan Wang, Meng Zhang, Peng Wang, Lei Zhang, Chao Yuan, Jianni Qi, Yu Qiao, Paul C. Kuo, and Chengjiang Gao. “NF-κB- and AP-1-mediated DNA looping regulates osteopontin transcription in endotoxin-stimulated murine macrophages.J Immunol 186, no. 5 (March 1, 2011): 3173–79. https://doi.org/10.4049/jimmunol.1003626.
Zhao W, Wang L, Zhang M, Wang P, Zhang L, Yuan C, et al. NF-κB- and AP-1-mediated DNA looping regulates osteopontin transcription in endotoxin-stimulated murine macrophages. J Immunol. 2011 Mar 1;186(5):3173–9.
Zhao, Wei, et al. “NF-κB- and AP-1-mediated DNA looping regulates osteopontin transcription in endotoxin-stimulated murine macrophages.J Immunol, vol. 186, no. 5, Mar. 2011, pp. 3173–79. Pubmed, doi:10.4049/jimmunol.1003626.
Zhao W, Wang L, Zhang M, Wang P, Zhang L, Yuan C, Qi J, Qiao Y, Kuo PC, Gao C. NF-κB- and AP-1-mediated DNA looping regulates osteopontin transcription in endotoxin-stimulated murine macrophages. J Immunol. 2011 Mar 1;186(5):3173–3179.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

March 1, 2011

Volume

186

Issue

5

Start / End Page

3173 / 3179

Location

United States

Related Subject Headings

  • p300-CBP Transcription Factors
  • Transcription, Genetic
  • Transcription Factor RelA
  • Transcription Factor AP-1
  • RNA, Small Interfering
  • Proto-Oncogene Proteins c-jun
  • Protein Binding
  • Osteopontin
  • Nucleic Acid Conformation
  • NF-kappa B