DGCR14 Induces Il17a Gene Expression through the RORγ/BAZ1B/RSKS2 Complex

TheDgcr14 /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 TH 17 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 ofDgcr14 mRNA enhanced RORγt-mediated transcriptional activity and facilitated TH 17 cell differentiation. Furthermore, knockdown of Dgcr14 reducedIl17a 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 theIl17a promoter during TH 17 cell differentiation. Knockdown ofBaz1b orRpS6ka3 also reducedIl17a mRNA expression, andBaz1b knockdown increased transcriptional suppressive histone marks (histone H3K9me3) on theIl17a promoter. My findings showed the roles of DGCR14, RSK2, and BAZ1B in the transcriptional regulation ofIl17a mRNA during TH 17 cell differentiation.