title: Notch1-mediated signaling induces MHC class II expression through activation of class II transactivator promoter III in mast cells.
abstract: Mast cells constitutively express Notch1 and Notch2 on the cell surface. Notch ligand Dll1 (Delta-like 1) stimulation induces MHC class II expression in mast cells and renders them as antigen-presenting cells. However, nothing is known about the mechanism by which Notch signaling induces MHC class II expression in mast cells. MHC class II genes are regulated by the class II transactivator (CIITA). In mice, transcription of the CIITA gene is controlled by three cell type-specific promoters (pI, pIII, and pIV). Here, we show that CIITA expression induced by Dll1 stimulation in mouse bone marrow-derived mast cells (BMMCs) depends critically on the signal mediated by Notch1 and that the most dominant promoter in Notch signaling-mediated CIITA expression in BMMCs is pIII, which is a lymphoid lineage-specific promoter. ChIP assays indicated that Notch signaling increased the binding of the transcription factor PU.1 to CIITA pIII in BMMCs. The knockdown of PU.1 expression using a specific siRNA suppressed Notch signaling-mediated CIITA expression, suggesting that PU.1 contributes to the expression of MHC class II induced by Notch signaling in mast cells. Furthermore, we show that a portion of freshly isolated splenic mast cells express MHC class II and that the most dominant promoter of CIITA in mast cells is pIII. These findings indicate that activation of CIITA pIII plays an important role in MHC class II expression in mast cells.
authors.affiliation: Atopy Allergy Research Center, Department of Immunology, Juntendo Univesity School of Medicine, Tokyo, Japan. nbnakano@juntendo.ac.jp
authors.forename: Nobuhiro
authors.initials: N
authors.lastname: Nakano
authors.forename: Chiharu
authors.initials: C
authors.lastname: Nishiyama
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Akemi
authors.initials: A
authors.lastname: Koyanagi
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000818:Animals; D015153:Blotting, Western; D016466:CHO Cells; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D018920:Coculture Techniques; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D050982:GATA1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D050989:GATA2 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008407:Mast Cells / Q000378:metabolism*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics*; D034622:RNA Interference; D051881:Receptor, Notch1 / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*
chemical_list: D002135:Calcium-Binding Proteins; C512925:Dlk1 protein, mouse; D050982:GATA1 Transcription Factor; D050989:GATA2 Transcription Factor; C494689:Gata1 protein, mouse; C494712:Gata2 protein, mouse; D000949:Histocompatibility Antigens Class II; D036341:Intercellular Signaling Peptides and Proteins; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D051881:Receptor, Notch1; D015534:Trans-Activators