Repression of GR-mediated expression of the tryptophan oxygenase gene by the SWI/SNF complex during liver development.

The chromatin remodeling complex, SWI/SNF, is known to regulate the transcription of several genes by altering the chromatin structure in an ATP-dependent manner. SWI/SNF exclusively contains BRG1 or BRM as an ATPase subunit. In the present study, we studied the role of SWI/SNF containing BRM or BRG1 in the expression of the liver-specific tryptophan oxygenase (TO) and tyrosine aminotransferase genes. Chromatin remodeling factors significantly repressed the expression of these genes induced by glucocorticoid receptor and dexamethasone. Since the repression was not reversed by trichostatin A treatment, it seemed to be independent of the well-known histone deacetylase pathway. Knock-down of BRG1 by small interfering RNA reversed the repression in primary fetal hepatocytes. These results support a model in which SWI/SNF containing BRG1 represses late stage-specific TO gene expression at an early stage of liver development.