Max Planck Institute for Molecular Genetics, Berlin, Germany.
Max Planck Institute for Molecular Genetics, Berlin, Germany
Life Sci Alliance. 2021 Aug 26;4(10). doi: 10.26508/lsa.202101080. Print 2021 Oct.
Glucocorticoids are stress hormones that elicit cellular responses by binding to the glucocorticoid receptor, a ligand-activated transcription factor. The exposure of cells to this hormone induces wide-spread changes in the chromatin landscape and gene expression. Previous studies have suggested that some of these changes are reversible whereas others persist even when the hormone is no longer around. However, when we examined chromatin accessibility in human airway epithelial cells after hormone washout, we found that the hormone-induced changes were universally reversed after 1 d. Moreover, priming of cells by a previous exposure to hormone, in general, did not alter the transcriptional response to a subsequent encounter of the same cue except for one gene, , that displays transcriptional memory manifesting itself as a more robust transcriptional response upon repeated hormone stimulation. Single-cell analysis revealed that the more robust response is driven by a higher probability of primed cells to activate and by a subset of cells that express the gene at levels that are higher than the induction levels observed for naïve cells.
糖皮质激素是应激激素，通过与糖皮质激素受体结合来引发细胞反应，后者是一种配体激活的转录因子。细胞暴露于这种激素会引起染色质景观和基因表达的广泛变化。先前的研究表明，其中一些变化是可逆的，而另一些变化即使在激素不再存在时也会持续存在。然而，当我们在激素洗脱后检查人呼吸道上皮细胞中的染色质可及性时，我们发现激素诱导的变化在 1 天后普遍逆转。此外，一般来说，先前暴露于激素会使细胞启动，而不会改变对随后遇到相同提示的转录反应，除了一个基因 ，它表现出转录记忆，表现为在重复激素刺激时产生更强烈的转录反应。单细胞分析表明，更强烈的反应是由更高概率的启动细胞激活 和表达基因的细胞亚群驱动的，其表达水平高于幼稚细胞观察到的诱导水平。
