title: Transcriptional regulation of the mouse CD11c promoter by AP-1 complex with JunD and Fra2 in dendritic cells.
abstract: CD11c, a member of the β(2) integrin family of adhesion molecule, is expressed on the surface of myeloid lineages and activated lymphoid cells and forms a heterodimeric receptor with CD18. We analyzed the mouse CD11c promoter structure to elucidate the transcriptional regulation in dendritic cells (DCs). By reporter assay, the -84/-65 region was identified to be essential for activity of the mouse CD11c promoter in the mouse bone marrow-derived (BM) DCs and monocyte cell line RAW264.7. An electrophoretic mobility shift assay using a number of antibodies against transcription factors revealed that the target region was recognized by a complex including JunD and Fra2, which are transcription factors belonging to the AP-1 family. The direct interaction of JunD and Fra2 with the CD11c promoter was further confirmed by a chromatin immunoprecipitation assay using CD11c-positive cells purified from BMDCs. Finally, mouse JunD and/or Fra2 siRNA was introduced into BMDCs to evaluate the involvement of these factors against CD11c transcription and found that Fra2 siRNA reduced cell surface expression level of CD11c. These results indicate that AP-1 composed with JunD and Fra2 protein plays a primary role in enhancing the transcription level of the CD11c gene in DC.
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.forename: Hokuto
authors.initials: H
authors.lastname: Yokoyama
authors.forename: Kanako
authors.initials: K
authors.lastname: Fukuyama
authors.forename: Nao
authors.initials: N
authors.lastname: Kitamura
authors.forename: Naomi
authors.initials: N
authors.lastname: Shimokawa
authors.forename: Keiko
authors.initials: K
authors.lastname: Maeda
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Kanada
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Ito
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Usui
authors.forename: Hideoki
authors.initials: H
authors.lastname: Ogawa
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
authors.forename: Makoto
authors.initials: M
authors.lastname: Nishiyama
authors.forename: Chiharu
authors.initials: C
authors.lastname: Nishiyama
mesh_terms: D000818:Animals; D001483:Base Sequence; D001665:Binding Sites / Q000235:genetics; D039521:CD11c Antigen / Q000235:genetics*; D002460:Cell Line; D002874:Chromosome Mapping; D017931:DNA Primers / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D051921:Fos-Related Antigen-2 / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D051379:Mice; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes / Q000737:chemistry / Q000378:metabolism; D011401:Promoter Regions, Genetic; D016755:Proto-Oncogene Proteins c-jun / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism*
chemical_list: D039521:CD11c Antigen; D017931:DNA Primers; D051921:Fos-Related Antigen-2; C497873:Fosl2 protein, mouse; D046912:Multiprotein Complexes; D016755:Proto-Oncogene Proteins c-jun; D034741:RNA, Small Interfering; D018808:Transcription Factor AP-1; C528955:junD protein, mouse