Ligand-dependent interaction between the estrogen receptor and the human homologues of SWI2/SNF2
Ligand-dependent interaction between the estrogen receptor and the human homologues of SWI2/SNF2
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DOI：
10.1016/s0378-1119(96)00785-8
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发表时间：
1997-03-25
期刊：
影响因子：
3.5
通讯作者：
Losson, R
中科院分区：
文献类型：
--
作者：
Ichinose, H;Garnier, JM;Losson, R
人SNF 2 α（或hbrm）和SNF 2 β（或BRG 1）蛋白先前已显示通过培养的人细胞中的核受体（NR）增强转录激活，并且存在于SWI/SNF复合物中，所述SWI/SNF复合物被认为通过促进染色质模板的重塑而参与转录控制。使用酵母双杂交系统，我们现在证明，在DNA依赖性ATP酶结构域之前的hSNF 2 α和hSNF 2 β的N-末端区域，特异性地与雌激素受体（ER）的区域相互作用，该区域包括配体结合结构域和配体依赖性激活功能AF-2。这些相互作用增加雌激素，但不是由ER AF-2拮抗剂羟基他莫昔芬。此外，缺乏AF-2活性的ER突变体不能与hSNF 2 α和β相互作用。这些结果表明，酵母SWI 2/SNF 2蛋白的人类同源物可能通过与AF-2激活结构域的相互作用参与ER在体内的转录增强，从而导致染色质模板的配体依赖性重塑。
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.