DGCR14 induces Il17a gene expression through the RORγ/BAZ1B/RSKS2 complex

Area of Science:

• Immunology
• Molecular Biology
• Genetics

Background:

• The DGCR14/ES2 gene resides in a region linked to DiGeorge syndrome.
• The precise function of the DGCR14 protein is not well understood.
• TH17 cells play a critical role in immune responses and autoimmune diseases.

Purpose of the Study:

• To elucidate the function of DGCR14 protein in immune cells.
• To investigate the role of DGCR14 in TH17 cell differentiation and function.
• To identify cofactors and mechanisms involved in DGCR14-mediated gene regulation.

Main Methods:

• Biochemical purification and mass spectrometry (MALDI-TOF MS) to identify RORγt interacting proteins.
• Overexpression and knockdown studies of Dgcr14 mRNA.
• Analysis of Il17a mRNA expression and RORγt transcriptional activity.
• Investigation of protein-protein interactions and recruitment to the Il17a promoter.
• Assessment of histone modifications at the Il17a promoter.

Main Results:

• DGCR14 protein functions as a coactivator for RORγt in TH17 cells.
• DGCR14 overexpression enhances RORγt activity and TH17 cell differentiation.
• DGCR14 knockdown reduces Il17a mRNA expression.
• DGCR14 interacts with RSK2 and BAZ1B, which are recruited to the Il17a promoter.
• Knockdown of RSK2 or BAZ1B also reduces Il17a mRNA expression, with BAZ1B affecting histone marks.

Conclusions:

• DGCR14 is a crucial coactivator for RORγt in TH17 cell differentiation.
• DGCR14, RSK2, and BAZ1B are integral components of the transcriptional machinery regulating Il17a.
• These findings shed light on the molecular mechanisms governing TH17 cell function and potential therapeutic targets.