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Papers In Press, published online ahead of print January 26, 2006
Microbiology and Medicine, Boston Universtiy School of Medicine, Boston, MA 02118
Corresponding Author: bnikol{at}bumc.bu.edu
Cytokine transcription is usually regulated by transcription factor binding and chromatin remodeling following an inducing signal. By contrast, data herein show the IL-1ß promoter assembles into a “poised” structure, as evidenced by nuclease accessibility and loss of core histones immediately surrounding the transcription start site. Strikingly, these properties do not change upon transcriptional activation by LPS. Furthermore, association of two key transcriptional activators, PU.1 and C/EBPß, is robust pre- and post-stimulation indicating the IL-1ß promoter is packaged into a non-transcribed but poised promoter architecture in cells capable of rapidly inducing IL-1ß. Monocyte stimulation causes recruitment of a third factor, IRF-4, to the IL-1ß enhancer. PU.1 phosphorylation at a CK2 kinase consensus element is required for this recruitment. We show that CK2 phosphorylates PU.1, CK2 inhibitors abrogate IL-1ß induction, and CK2 inducibly associates with the IL-1ß enhancer. Taken together, these data indicate a novel two-step mechanism for IL-1ß transcription: 1) formation of a poised chromatin architecture, and 2) phosphorylation of an enhancer-bound factor that recruits other activators. We propose this poised structure may generally characterize rapidly activated genes.
J. Biol. Chem, 10.1074/jbc.M510700200
Submitted on September 30, 2005
Revised on January 17, 2006
Accepted on January 26, 2006
The IL-1
gene is transcribed from a poised promoter architecture in monocytes
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