The DUX4 protein is a co‐repressor of the progesterone and glucocorticoid nuclear receptors

DUX4 is a transcription factor required during early embryonic development in placental mammals. In this work, we provide evidence that DUX4 is a co‐repressor of nuclear receptors (NRs) of progesterone (PR) and glucocorticoids (GR). The DUX4 C‐ter and N‐ter regions, including the nuclear localization signals and homeodomain motifs, contribute to the co‐repressor activity of DUX4 on PR and GR. Immunoprecipitation studies, using total protein extracts of cells expressing tagged versions of DUX4 and GR, support that these proteins are physically associated. Our studies suggest that DUX4 could modulate gene expression by co‐regulating the activity of hormone NRs. This is the first report highlighting a potential endocrine role for DUX4. DUX4 is a co‐repressor of the progesterone and glucocorticoid nuclear receptors (NRs). Hormones (H; blue dots) bind their corresponding NRs, activating (+) the expression of a reporter target gene. The activity of the NRs is repressed (−) in the presence of DUX4 (red arrow). Cy, cytoplasm; Nu, nucleus.