Characterization of short range DNA looping in endotoxin-mediated transcription of the murine inducible nitric-oxide synthase (iNOS) gene.
Journal Article (Journal Article)
The local structural properties and spatial conformations of chromosomes are intimately associated with gene expression. The spatial associations of critical genomic elements in inducible nitric-oxide synthase (iNOS) transcription have not been previously examined. In this regard, the murine iNOS promoter contains 2 NF-kappaB binding sites (nt -86 and nt -972) that are essential for maximal transactivation of iNOS by LPS. Although AP-1 is commonly listed as an essential transcription factor for LPS-mediated iNOS transactivation, the relationship between AP-1 and NF-kappaB in this setting is not well studied. In this study using a model of LPS-stimulated ANA-1 murine macrophages, we demonstrate that short range DNA looping occurs at the iNOS promoter. This looping requires the presence of AP-1, c-Jun, NF-kappaB p65, and p300-associated acetyltransferase activity. The distal AP-1 binding site interacts via p300 with the proximal NF-kappaB binding site to create this DNA loop to participate in iNOS transcription. Other geographically distant AP-1 and NF-kappaB sites are certainly occupied, but selected sites are critical for iNOS transcription and the formation of the c-Jun, p65, and p300 transcriptional complex. In this "simplified" model of murine iNOS promoter, numerous transcription factors recognize and bind to various response elements, but these locales do not equally contribute to iNOS gene transcription.
Full Text
Duke Authors
Cited Authors
- Guo, H; Mi, Z; Kuo, PC
Published Date
- September 12, 2008
Published In
Volume / Issue
- 283 / 37
Start / End Page
- 25209 - 25217
PubMed ID
- 18596035
Pubmed Central ID
- PMC2533077
International Standard Serial Number (ISSN)
- 0021-9258
Digital Object Identifier (DOI)
- 10.1074/jbc.M804062200
Language
- eng
Conference Location
- United States