Glucocorticoid signaling induces transcriptional memory and universally reversible chromatin changes.
Glucocorticoid signaling induces transcriptional memory and universally reversible chromatin changes.
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DOI：
10.26508/lsa.202101080
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发表时间：
2021-10
影响因子：
4.4
通讯作者：
Meijsing SH
中科院分区：
文献类型：
--
作者：
Bothe M;Buschow R;Meijsing SH
糖皮质激素是一种应激激素，可以引起各种细胞反应。这些反应通常是可逆的；然而，在某些情况下，以前的暴露会被“记住”，并影响对随后的荷尔蒙遭遇的反应。糖皮质激素是一种应激激素，通过与糖皮质激素受体(一种配体激活的转录因子)结合来引发细胞反应。细胞暴露在这种激素下会引起染色质景观和基因表达的广泛变化。以前的研究表明，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的情况下也会持续。然而，当我们检查激素洗脱后人类呼吸道上皮细胞染色质的可及性时，我们发现激素诱导的变化在1d后普遍被逆转。此外，通常情况下，通过先前接触激素来启动细胞并不会改变对随后遇到相同线索的转录反应，除了一个基因ZBTB16，它表现出转录记忆，表现为重复激素刺激时更强大的转录反应。单细胞分析显示，更强劲的反应是由启动细胞激活ZBTB16的更高概率驱动的，以及由表达该基因的水平高于观察到的幼稚细胞的诱导水平的细胞子集驱动的。
Glucocorticoids are stress hormones that elicit various cellular responses. These responses are typically reversible; however, in some instances, a previous exposure is “remembered” and influences the response to a subsequent hormone encounter. 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, ZBTB16, 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 ZBTB16 and by a subset of cells that express the gene at levels that are higher than the induction levels observed for naïve cells.