RT Journal Article
SR Electronic
T1 Glucocorticoid signaling induces transcriptional memory and universally reversible chromatin changes
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101080
DO 10.26508/lsa.202101080
VO 4
IS 10
A1 Melissa Bothe
A1 René Buschow
A1 Sebastiaan H Meijsing
YR 2021
UL https://www.life-science-alliance.org/content/4/10/e202101080.abstract
AB 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.