Ligand-dependent interaction between the estrogen receptor and the human homologues of SWI2/SNF2

The human SNF2 alpha (or hbrm) and SNF2 beta (or BRG1) proteins have previously been shown to enhance transcriptional activation by nuclear receptors (NRs) in cultured human cells, and to be present in SWI/SNF complexes which are thought to be involved in control of transcription by facilitating remodelling of chromatin templates. Using the yeast two-hybrid system, we now demonstrate that the N-terminal regions of hSNF2 alpha and hSNF2 beta, preceding the DNA-dependent ATPase domain, specifically interact with the region of the estrogen receptor (ER) which includes the ligand binding domain and the ligand-dependent activation function AF-2. These interactions are increased by estrogen, but not by the ER AF-2 antagonist hydroxytamoxifen. Furthermore, mutants of ER that lack AF-2 activity are unable to interact with hSNF2 alpha and -beta. These results suggest that the human homologues of the yeast SWI2/SNF2 protein may participate in the enhancement of transcription by the ER in vivo through interactions with the AF-2 activating domain, thus leading to ligand-dependent remodelling of chromatin templates.