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Article

Role of Non-Coding Regulatory Elements in the Control of GR-Dependent Gene Expression

Laboratory of Pharmacogenomics, Department of Molecular Neuropharmacology, Maj Institute of Pharmacology, Polish Academy of Sciences, 31-343 Krakow, Poland
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Authors to whom correspondence should be addressed.
Academic Editor: Michał Dąbrowski
Int. J. Mol. Sci. 2021, 22(8), 4258; https://doi.org/10.3390/ijms22084258
Received: 15 March 2021 / Revised: 6 April 2021 / Accepted: 8 April 2021 / Published: 20 April 2021
(This article belongs to the Special Issue Functions of Non-coding DNA Regions)
The glucocorticoid receptor (GR, also known as NR3C1) coordinates molecular responses to stress. It is a potent transcription activator and repressor that influences hundreds of genes. Enhancers are non-coding DNA regions outside of the core promoters that increase transcriptional activity via long-distance interactions. Active GR binds to pre-existing enhancer sites and recruits further factors, including EP300, a known transcriptional coactivator. However, it is not known how the timing of GR-binding-induced enhancer remodeling relates to transcriptional changes. Here we analyze data from the ENCODE project that provides ChIP-Seq and RNA-Seq data at distinct time points after dexamethasone exposure of human A549 epithelial-like cell line. This study aimed to investigate the temporal interplay between GR binding, enhancer remodeling, and gene expression. By investigating a single distal GR-binding site for each differentially upregulated gene, we show that transcriptional changes follow GR binding, and that the largest enhancer remodeling coincides in time with the highest gene expression changes. A detailed analysis of the time course showed that for upregulated genes, enhancer activation persists after gene expression changes settle. Moreover, genes with the largest change in EP300 binding showed the highest expression dynamics before the peak of EP300 recruitment. Overall, our results show that enhancer remodeling may not directly be driving gene expression dynamics but rather be a consequence of expression activation. View Full-Text
Keywords: glucocorticoid receptor; GR; NR3C1; enhancer sequences; expression regulation; EP300; histone modifications; ENCODE; RNA-Seq; ChIP-Seq glucocorticoid receptor; GR; NR3C1; enhancer sequences; expression regulation; EP300; histone modifications; ENCODE; RNA-Seq; ChIP-Seq
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MDPI and ACS Style

Borczyk, M.; Zieba, M.; Korostyński, M.; Piechota, M. Role of Non-Coding Regulatory Elements in the Control of GR-Dependent Gene Expression. Int. J. Mol. Sci. 2021, 22, 4258. https://doi.org/10.3390/ijms22084258

AMA Style

Borczyk M, Zieba M, Korostyński M, Piechota M. Role of Non-Coding Regulatory Elements in the Control of GR-Dependent Gene Expression. International Journal of Molecular Sciences. 2021; 22(8):4258. https://doi.org/10.3390/ijms22084258

Chicago/Turabian Style

Borczyk, Malgorzata, Mateusz Zieba, Michał Korostyński, and Marcin Piechota. 2021. "Role of Non-Coding Regulatory Elements in the Control of GR-Dependent Gene Expression" International Journal of Molecular Sciences 22, no. 8: 4258. https://doi.org/10.3390/ijms22084258

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