biostudies-literatureCharrier ANIA NIH HHSNational Institute of Diabetes and Digestive and Kidney DiseasesNIDDK NIH HHSNational Institute on Aginge0294003https://www.ebi.ac.uk/biostudies/studies/S-EPMC11115250biostudies-literatureUnknown19(5)Cofactors interacting with PPARγ can regulate adipogenesis and adipocyte metabolism by modulating the transcriptional activity and selectivity of PPARγ signaling. ZFP407 was previously demonstrated to regulate PPARγ target genes such as GLUT4, and its overexpression improved glucose homeostasis in mice. Here, using a series of molecular assays, including protein-interaction studies, mutagenesis, and ChIP-seq, ZFP407 was found to interact with the PPARγ/RXRα protein complex in the nucleus of adipocytes. Consistent with this observation, ZFP407 ChIP-seq peaks significantly overlapped with PPARγ ChIP-seq peaks, with more than half of ZFP407 peaks overlapping with PPARγ peaks. Transcription factor binding motifs enriched in these overlapping sites included CTCF, RARα/RXRγ, TP73, and ELK1, whicPloS oneMolecular regulation of PPARγ/RXRα signaling by the novel cofactor ZFP407.PMC11115250R01 DK119305T32 AG071474R01 AG058066DK119305U01 AG058654Buchner DACharrier AMain LGhanta SVOckunzzi JfalseMolecular regulation of PPARγ/RXRα signaling by the novel cofactor ZFP407.Cofactors interacting with PPARγ can regulate adipogenesis and adipocyte metabolism by modulating the transcriptional activity and selectivity of PPARγ signaling. ZFP407 was previously demonstrated to regulate PPARγ target genes such as GLUT4, and its overexpression improved glucose homeostasis in mice. Here, using a series of molecular assays, including protein-interaction studies, mutagenesis, and ChIP-seq, ZFP407 was found to interact with the PPARγ/RXRα protein complex in the nucleus of adipocytes. Consistent with this observation, ZFP407 ChIP-seq peaks significantly overlapped with PPARγ ChIP-seq peaks, with more than half of ZFP407 peaks overlapping with PPARγ peaks. Transcription factor binding motifs enriched in these overlapping sites included CTCF, RARα/RXRγ, TP73, and ELK1, whic2024-01-01T00:00:00Z20242026-06-02T06:10:42.157Z2026-04-15T03:09:53.112ZS-EPMC111152503878115710.1371/journal.pone.0294003