ニシオ　ジュンコ   Nishio Junko   西尾　純子    所属   東邦大学  医学部 医学科    職種   准教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Regulation of cooperative function of the Il12b enhancer and promoter by the interferon regulatory factors 3 and 5.
掲載誌名	正式名：Biochemical and biophysical research communications
掲載区分	国外
巻・号・頁	430(1),pp.95-100
著者・共著者	Ryuji Koshiba,Hideyuki Yanai,Atsushi Matsuda,Ayana Goto,Akira Nakajima,Hideo Negishi,Junko Nishio,Stephen T Smale,Tadatsugu Taniguchi
発行年月	2013/01/04
概要	The regulation of the Il12b gene, encoding the shared p40 subcomponent for IL-12 and IL-23, is critical for innate immune responses and subsequent T cell polarization. This gene is robustly induced upon Toll-like receptor (TLR) stimulation, wherein an enhancer located 10kb upstream of the transcription start site is required for promoter activity; however, the underlying mechanisms that regulate this enhancer in cooperation with the promoter has remained elusive. We show here that the Il12b enhancer contains functional ISREs for recognition by interferon regulatory factors (IRFs), and provide evidence that TLR-activated IRF5 mediates cooperativity of the enhancer with the promoter which also contains ISREs. By contrast, IRF3 activated by cytosolic RIG-I-like receptor (RLR) signaling binds to these ISREs and causes gene suppression. Consistently, IRF5 binding is accompanied with chromatin remodeling of both regulatory regions and the formation of a productive transcriptional complex containing other transcription factors, whereas these events are inhibited by IRF3 binding. We show that the ISREs embedded in the enhancer are indeed critical for its activation by IRF5. We also adduce evidence that the 5' sequences of the enhancer and promoter ISREs, all of which deviate from consensus ISREs, critically affect the function of IRF3. The dual commitment of these IRFs in the regulation of the Il12b enhancer and promoter is unique and may have implications for understanding the evolution of this gene.
DOI	10.1016/j.bbrc.2012.11.006
PMID	23154183