Cbfβ controls DNA folding to regulate different Il4 and Il13 gene activity in Th2 immune cells

Core-binding factor beta (Cbfβ) is identified as a specific inducer of IL-13 while inhibiting IL-4 expression.

• Th2 cells are central to type 2 immune responses through the production of type 2 cytokines like IL-4 and IL-13.
• GATA3 is essential for type 2 cytokine production but does not act alone in regulating their expression.
• A CRISPR-Cas9 screen targeting 2,394 mouse transcription factors identified Cbfβ as a key regulator of IL-13.
• Cbfβ's effect on IL-13 production is independent of GATA3 induction and confirmed in both laboratory and living organisms.
• Cbfβ enhances chromatin accessibility at the HS-2 site of the Il13 promoter, indicating its role in DNA regulation.
• Deletion of Cbfβ reduces DNA looping between HS-2 and other enhancers, suggesting a mechanism for its regulatory function.

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