Ligand-dependent interaction between the estrogen receptor and the human homologues of SWI2/SNF2.
The human SNF2alpha (or hbrm) and SNF2beta (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 hSNF2alpha and hSNF2beta, 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 hSNF2alpha 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.
Ichinose
H
H
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Collège de France, Illkirch.
Garnier
J M
JM
Chambon
P
P
Losson
R
R
D001665:Binding Sites; D017124:Conserved Sequence; D004265:DNA Helicases; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005786:Gene Expression Regulation; D006801:Humans; D008024:Ligands; D009687:Nuclear Proteins; D011485:Protein Binding; D011960:Receptors, Estrogen / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology; D014157:Transcription Factors / Q000378:metabolism*
D004268:DNA-Binding Proteins; D008024:Ligands; D009687:Nuclear Proteins; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; C499336:SMARCA1 protein, human; C084011:SMARCA2 protein, human; D014157:Transcription Factors; D013629:Tamoxifen; D004958:Estradiol; C084108:SMARCA4 protein, human; D004265:DNA Helicases