Abstract
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.
Highlights
activating protein-1 (AP-1) is commonly listed as an essential transcription factor for transcriptional coactivator p300 interacts with several tran
In this study and AP-1. p300 coactivates transcription via its histone acetylusing a model of LPS-stimulated ANA-1 murine macrophages, transferase activity, mediates interactions with the basal tranwe demonstrate that short range DNA looping occurs at the scription machinery, and is a key scaffolding protein in the foriNOS promoter
The murine inducible nitric-oxide synthase (iNOS) promoter contains only two requisite NF-B binding sites and was chosen as a simpler model for investigation of DNA looping that may occur among the various NF-B and AP-1 sites [1]
Summary
AP-1 is commonly listed as an essential transcription factor for transcriptional coactivator p300 interacts with several tran-. P300 coactivates transcription via its histone acetylusing a model of LPS-stimulated ANA-1 murine macrophages, transferase activity, mediates interactions with the basal tranwe demonstrate that short range DNA looping occurs at the scription machinery, and is a key scaffolding protein in the foriNOS promoter. Our results indicate that p300 bridges AP-1, c-Jun (nt Ϫ1069), and NF-B p65 (nt Ϫ86) to form a DNA loop to initiate iNOS gene transcription.
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