title: Critical Role of Transcription Factor PU.1 in the Function of the OX40L/TNFSF4 Promoter in Dendritic Cells.
abstract: PU.1 is a hematopoietic lineage-specific transcription factor belonging to the Ets family. We investigated the role of PU.1 in the expression of OX40L in dendritic cells (DCs), because the regulatory mechanism of cell type-specific expression of OX40L, which is mainly restricted to antigen-presenting cells, is largely unknown despite the critical involvement in Th2 and Tfh development. PU.1 knockdown decreased the expression of OX40L in mouse DCs. Chromatin immunoprecipitation (ChIP) assays demonstrated that PU.1 constitutively bound to the proximal region of the OX40L promoter. Reporter assays and electrophoretic mobility shift assays revealed that PU.1 transactivated the OX40L promoter through direct binding to the most-proximal Ets motif. We found that this Ets motif is conserved between mouse and human, and that PU.1 bound to the human OX40L promoter in ChIP assay using human monocyte-derived DCs. ChIP assays based on ChIP-seq datasets revealed that PU.1 binds to several sites distant from the transcription start site on the OX40L gene in addition to the most-proximal site in mouse DCs. In the present study, the structure of the OX40L promoter regulated by PU.1 is determined. It is also suggested that PU.1 is involved in mouse OX40L expression via multiple binding sites on the gene.
authors.affiliation: Laboratory of Molecular Biology and Immunology, Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo, 125-8585, Japan.|Atopy Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.|Research Fellow of Japan Society for the Promotion of Science, 5-3-1 Koujimachi, Chiyoda-ku, Tokyo 102-0083.
authors.forename: Takuya
authors.initials: T
authors.lastname: Yashiro
authors.affiliation: Atopy Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Mutsuko
authors.initials: M
authors.lastname: Hara
authors.affiliation: Atopy Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.affiliation: Atopy Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.affiliation: Laboratory of Molecular Biology and Immunology, Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 6-3-1 Niijuku, Katsushika-ku, Tokyo, 125-8585, Japan.|Atopy Research Center, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan.
authors.forename: Chiharu
authors.initials: C
authors.lastname: Nishiyama
mesh_terms: D000818:Animals; D003713:Dendritic Cells / Q000502:physiology*; D005260:Female; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D059372:Nucleotide Motifs; D053278:OX40 Ligand / Q000235:genetics / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D024363:Transcription Initiation Site; D015533:Transcriptional Activation; D048069:Tumor Necrosis Factors / Q000235:genetics* / Q000378:metabolism; D000099232:Proto-Oncogene Protein Spi-1
chemical_list: D008562:Membrane Glycoproteins; D053278:OX40 Ligand; D011518:Proto-Oncogene Proteins; D015534:Trans-Activators; D048069:Tumor Necrosis Factors; D000099232:Proto-Oncogene Protein Spi-1; C089251:TNFSF4 protein, human; C504586:Tnfsf4 protein, mouse