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

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Zhao, W; Wang, L; Zhang, M; Wang, P; Zhang, L; Yuan, C; Qi, J; Qiao, Y; Kuo, PC; Gao, C

Published Date

  • March 2011

Published In

Volume / Issue

  • 186 / 5

Start / End Page

  • 3173 - 3179

PubMed ID

  • 21257959

Pubmed Central ID

  • 21257959

Electronic International Standard Serial Number (EISSN)

  • 1550-6606

International Standard Serial Number (ISSN)

  • 0022-1767

Digital Object Identifier (DOI)

  • 10.4049/jimmunol.1003626

Language

  • eng