Steroid hormones are pivotal modulators of pathophysiological processes in many organs, where they interact with nuclear receptors to regulate gene transcription. However, our understanding of hormone action at the single cell level remains incomplete. Here, we focused on estrogen stimulation of the well-characterized GREB1 and MYC target genes that revealed large differences in cell-by-cell responses, and, more interestingly, between alleles within the same cell, both over time and hormone concentration. We specifically analyzed the role of receptor level and activity state during allele-by-allele regulation and found that neither receptor level nor activation status are the determinant of maximal hormonal response, indicating that additional pathways are potentially in place to modulate cell- and allele-specific responses. Interestingly, we found that a small molecule inhibitor of the arginine methyltransferases CARM1 and PRMT6 was able to increase, in a gene specific manner, the number of active alleles/cell before and after hormonal stimulation, suggesting that mechanisms do indeed exist to modulate hormone receptor responses at the single cell and allele level.

中文翻译：

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雌激素在各个等位基因上的转录独立于受体水平和活性构象，但可以通过共激活因子的活性进行调节。

类固醇激素是许多器官病理生理过程的关键调节剂，它们在其中与核受体相互作用以调节基因转录。但是，我们对激素在单细胞水平上的作用的了解仍然不完整。在这里，我们集中研究了特征明确的GREB1和MYC靶基因的雌激素刺激，这些基因揭示了逐细胞反应的较大差异，并且更有趣的是，同一细胞内的等位基因之间随时间和激素浓度存在很大差异。我们专门分析了等位基因-等位基因调节过程中受体水平和活性状态的作用，发现受体水平和激活状态均不是最大激素反应的决定因素，这表明可能存在其他途径来调节细胞和等位基因-具体的回应。有趣的是