“Master” transcription factors are the gatekeepers of lineage identity. As such, they have been a major focus of efforts to manipulate cell fate for therapeutic purposes. The ETS transcription factor PU. 1 has a potent ability to confer macrophage phenotypes on cells already committed to a different lineage, but how it overcomes the presence of other master regulators is not known. The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is the master regulator of the adipose lineage, and its genomic binding pattern in adipocytes is well characterized. Here we show that, when expressed at macrophage levels in mature adipocytes, PU. 1 bound a large fraction of its macrophage sites, where it induced chromatin opening and the expression of macrophage target genes. Strikingly, PU. 1 markedly reduced the genomic binding of PPARγ without changing its abundance. PU. 1 expression repressed genes with nearby adipocyte-specific PPARγ binding sites, while a common macrophage-adipocyte gene expression program was retained. Together, these data reveal unexpected lability within the adipocyte PPARγ cistrome and show that, even in terminally differentiated cells, PU. 1 can remodel the cistrome of another master regulator.