The glucocorticoid receptor β isoform can mediate transcriptional repression by recruiting histone deacetylases
The glucocorticoid receptor β isoform can mediate transcriptional repression by recruiting histone deacetylases
复制标题
DOI：
10.1016/j.jaci.2007.09.010
复制
发表时间：
2008-01-01
影响因子：
14.2
通讯作者：
Lavender, Paul
中科院分区：
文献类型：
--
作者：
Kelly, Audrey;Bowen, Holly;Lavender, Paul
背景资料：糖皮质激素受体（GR）能够通过多种机制参与转录调节，其中之一涉及DNA结合和调节辅因子的募集。受体的最佳研究形式是777-氨基酸α和742-氨基酸β变体。β亚型，它不结合皮质醇在人类subjects，已被提出是一个显性负抑制剂的转录激活能力GR α isoform.Objective：GR α有两个转录激活和抑制的作用。我们希望确定GR β对通常被糖皮质激素转录抑制的基因的影响。我们研究了与哮喘表型相关的IL 5和IL 13。方法：我们采用瞬时转染系统和免疫共沉淀实验来确定GR β是否对人IL 5和IL 13基因的启动子具有抑制活性。结果：GRP能够作为细胞因子基因的转录抑制因子，并通过募集组蛋白去乙酰化酶复合物来介导其功能。结论：GR α和GR β以类似的方式作用于IL 5和IL 13启动子，用于抑制转录。在这种情况下，GR β不作为GR α的显性负抑制剂。
Background: The glucocorticoid receptor (GR) is able to participate in regulation of transcription by a variety of mechanisms, one of which involves DNA binding and recruitment of regulatory cofactors. The best-studied forms of the receptor are the 777-amino-acid alpha and the 742-amino-acid beta variants. The beta isoform, which does not bind cortisol in human subjects, has been proposed to be a dominant-negative inhibitor of the transcriptional activation-competent GR alpha isoform.Objective: GR alpha has roles in both transcriptional activation and repression. We wished to determine the influence of GR beta on genes that are normally transcriptionally repressed by glucocorticoids. We studied IL5 and IL13, which both contribute to the asthmatic phenotype.Methods: We used transient transfection systems and coimmunoprecipitation experiments to determine whether GR beta has repressive activity on the promoters of the human IL5 and IL13 genes.Results: GRP is able to act as a transcriptional repressor of cytokine genes and mediates its function through the recruitment of histone deacetylase complexes.Conclusion: GR alpha and GR beta act in a similar manner on IL5 and IL13 promoters, serving to repress transcription. In this circumstance GR beta does not act as a dominant-negative inhibitor of GR alpha.