A transcriptional cofactor GRIP1 drives PPARγ DNA binding and p300-dependent enhancer activity during homeostatic macrophage polarization.

GRIP1 is essential for PPARγ DNA binding and enhancer activity during homeostatic macrophage polarization, with its deletion reducing PPARγ target gene expression.

• Why it matters: Understanding how PPARγ activates gene expression without ligand binding addresses a key gap in macrophage biology and inflammation regulation, which is vital for tissue health.
• What they did: The study used macrophages treated with IL4 and rosiglitazone, comparing PPARγ activity with and without GRIP1 or NCoA2, and assessed genome-wide DNA binding and gene expression.
• The result: GRIP1 deletion dramatically decreases PPARγ DNA binding and target gene transcription, indicating GRIP1's critical role in unliganded PPARγ function and macrophage homeostasis.