Cbfβ regulates DNA looping at the Il4-Il13 loci to control their differential expression in Th2 cells.

Cbfβ specifically induces IL-13 while simultaneously inhibiting IL-4 expression in mouse Th2 cells, with effects confirmed in vitro and in vivo.

• Why it matters: GATA3 is essential but not sufficient for type 2 cytokine production, so additional transcriptional regulators and their mechanisms for IL-4 versus IL-13 control are needed.
• What they did: A CRISPR-Cas9 screen using a retroviral sgRNA library targeting 2,394 mouse transcription factors and cofactors identified Cbfβ; Hi-TrAC and chromatin accessibility assays tested Il13 promoter looping and HS-2 accessibility.
• The result: Cbfβ binds the Il13 promoter via the Cbfβ/Runx complex, increases HS-2 accessibility, and reduces enhancer-promoter DNA looping when deleted, enabling IL-13 transcription.