title: DGCR14 induces Il17a gene expression through the RORγ/BAZ1B/RSKS2 complex.
abstract: The Dgcr14/Es2 gene is located in a chromosomal region the loss of which has been associated with DiGeorge syndrome, a cause of immunodeficiency, heart defects, and skeletal abnormalities. However, the role of DGCR14 protein remains to be elucidated. Here, I found that DGCR14 protein acts as a coactivator of RORγt in TH17 cells. Biochemical purification of the RORγ coregulator complex allowed me to identify the associated DGCR14 protein by matrix-assisted laser desorption ionization-time of flight mass spectrometry. Overexpression of Dgcr14 mRNA enhanced RORγt-mediated transcriptional activity and facilitated TH17 cell differentiation. Furthermore, knockdown of Dgcr14 reduced Il17a mRNA expression. I also found that DGCR14 associated with ribosomal S6 kinase 2 (RSK2, also called RpS6ka3) and BAZ1B, both of which were recruited to the Il17a promoter during TH17 cell differentiation. Knockdown of Baz1b or RpS6ka3 also reduced Il17a mRNA expression, and Baz1b knockdown increased transcriptional suppressive histone marks (histone H3K9me3) on the Il17a promoter. My findings showed the roles of DGCR14, RSK2, and BAZ1B in the transcriptional regulation of Il17a mRNA during TH17 cell differentiation.
authors.affiliation: Division of Biochemistry, Department of Biomedical Sciences, Nihon University School of Medicine, Itabashi-ku, and Department of Microbiology and Immunology, School of Medicine, Keio University, Shinjuku-ku, Tokyo, Japan takada.ichiro@nihon-u.ac.jp.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Takada
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics; D006657:Histones / Q000378:metabolism; D006801:Humans; D020381:Interleukin-17 / Q000235:genetics*; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics*; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3 / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D000092468:Bromodomain Containing Proteins
chemical_list: D006657:Histones; D020381:Interleukin-17; D009687:Nuclear Proteins; D057132:Nuclear Receptor Subfamily 1, Group F, Member 3; D012333:RNA, Messenger; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D014157:Transcription Factors; C116750:BAZ1B protein, human; D000092468:Bromodomain Containing Proteins; C485505:Baz1b protein, mouse; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3