SETD1A/COMPASS a locus-specific co-regulator of the Glucocorticoid Receptor in murine macrophages

Glucocorticoids (GCs) are potent anti-inflammatory drugs, widely prescribed. They repress pro-inflammatory genes and induce anti-inflammatory and metabolic genes by binding to the glucocorticoid receptor (GR). Here we try to decipher the molecular mechanism of gene repression and activation in the same cell type by profiling nuclear interaction partners of the GR. We found that GR interacts with the COMPASS/SETD1A complex, which is recruited to activating GR binding sites (GBS). A Setd1a hypermorphic cell line does not show impaired GR-dependent H3K4me2/me3 dynamics, but dampens GR-dependent gene activation. A Setd1a mutant with defective histone methyltransferase activity on the other hand does not show impaired GR-dependent gene activation, pointing towards a COMPASS/SETD1A function at GR enhancers that is independent on its histone methyl transferase activity.      «

Glucocorticoids (GCs) are potent anti-inflammatory drugs, widely prescribed. They repress pro-inflammatory genes and induce anti-inflammatory and metabolic genes by binding to the glucocorticoid receptor (GR). Here we try to decipher the molecular mechanism of gene repression and activation in the same cell type by profiling nuclear interaction partners of the GR. We found that GR interacts with the COMPASS/SETD1A complex, which is recruited to activating GR binding sites (GBS). A Setd1a hyper...     »