LPS and poly I:C induce chromatin modifications at a novel upstream region of the IL-23 p19 promoter.
IL-23, a heterodimer of IL-12 p40 and IL-23 p19, is critical for an effective immune response to many infections and has been implicated in several autoimmune diseases, however, little is known about the regulation of IL-23 gene expression in monocytes. We found that poly I:C, LPS, flagellin, and zymogen activated significant IL-23 production in primary human monocytes. Using chromatin immunoprecipitation, we found that a distal upstream region of the IL-23 p19 promoter at -601 to -521 underwent extensive histone modifications in response to stimuli. This distal region of the promoter is not highly conserved between species and has not been previously implicated in the regulation of IL-23 expression. Knockdown of CBP markedly decreased IL-23 p19 responses to poly I:C but had a less dramatic effect on LPS responses, confirming different chromatin responses to these two stimuli. Our data suggest that one of the mechanisms regulating IL-23 expression is the regulation of histone modifications at this distal upstream region of the promoter.
Garrett
Stacey
S
The Division of Allergy and Immunology, The Children's Hospital of Philadelphia, ARC 1216, 34th St. and Civic Ctr. Blvd., Philadelphia, PA 19104, USA.
Fitzgerald
Michael C
MC
Sullivan
Kathleen E
KE
D001483:Base Sequence; D002478:Cells, Cultured; D002843:Chromatin / Q000187:drug effects* / Q000235:genetics*; D017931:DNA Primers / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D053760:Interleukin-23 Subunit p19 / Q000096:biosynthesis / Q000235:genetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008969:Molecular Sequence Data; D009000:Monocytes / Q000187:drug effects / Q000276:immunology; D011070:Poly I-C / Q000494:pharmacology*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D012689:Sequence Homology, Nucleic Acid; D051193:Toll-Like Receptors / Q000378:metabolism
D002843:Chromatin; D017931:DNA Primers; D053760:Interleukin-23 Subunit p19; D008070:Lipopolysaccharides; D051193:Toll-Like Receptors; D011070:Poly I-C