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Genomic regulation of Krüppel-like-factor family members by corticosteroid receptors in the rat brain
Hippocampal mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) mediate glucocorticoid hormone (GC) action in the hippocampus. These receptors bind to glucocorticoid responsive elements (GREs) within target genes, eliciting transcriptional effects in response to stress and circadian...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024234/ https://www.ncbi.nlm.nih.gov/pubmed/36942087 http://dx.doi.org/10.1016/j.ynstr.2023.100532 |
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author | Kennedy, Clare L.M. Price, Emily M. Mifsud, Karen R. Salatino, Silvia Sharma, Eshita Engledow, Simon Broxholme, John Goss, Hannah M. Reul, Johannes M.H.M. |
author_facet | Kennedy, Clare L.M. Price, Emily M. Mifsud, Karen R. Salatino, Silvia Sharma, Eshita Engledow, Simon Broxholme, John Goss, Hannah M. Reul, Johannes M.H.M. |
author_sort | Kennedy, Clare L.M. |
collection | PubMed |
description | Hippocampal mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) mediate glucocorticoid hormone (GC) action in the hippocampus. These receptors bind to glucocorticoid responsive elements (GREs) within target genes, eliciting transcriptional effects in response to stress and circadian variation. Until recently, little was known about the genome-wide targets of hippocampal MRs and GRs under physiological conditions. Following on from our genome-wide MR and GR ChIP-seq and Ribo-Zero RNA-seq studies on rat hippocampus, we investigated the Krüppel-like factors (KLFs) as targets of MRs and GRs throughout the brain under circadian variation and after acute stress. In particular, Klf2, Klf9 and Klf15 are known to be stress and/or GC responsive and play a role in neurobiological processes including synaptic plasticity and neuronal differentiation. We found increased binding of MR and GR to GREs within Klf2, Klf9 and Klf15 in the hippocampus, amygdala, prefrontal cortex, and neocortex after acute stress and resulting from circadian variation, which was accompanied by upregulation of corresponding hnRNA and mRNA levels. Adrenalectomy abolished transcriptional upregulation of specific Klf genes. These results show that MRs and GRs regulate Klf gene expression throughout the brain following exposure to acute stress or in response to circadian variation, likely alongside other transcription factors. |
format | Online Article Text |
id | pubmed-10024234 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-100242342023-03-19 Genomic regulation of Krüppel-like-factor family members by corticosteroid receptors in the rat brain Kennedy, Clare L.M. Price, Emily M. Mifsud, Karen R. Salatino, Silvia Sharma, Eshita Engledow, Simon Broxholme, John Goss, Hannah M. Reul, Johannes M.H.M. Neurobiol Stress Original Research Article Hippocampal mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) mediate glucocorticoid hormone (GC) action in the hippocampus. These receptors bind to glucocorticoid responsive elements (GREs) within target genes, eliciting transcriptional effects in response to stress and circadian variation. Until recently, little was known about the genome-wide targets of hippocampal MRs and GRs under physiological conditions. Following on from our genome-wide MR and GR ChIP-seq and Ribo-Zero RNA-seq studies on rat hippocampus, we investigated the Krüppel-like factors (KLFs) as targets of MRs and GRs throughout the brain under circadian variation and after acute stress. In particular, Klf2, Klf9 and Klf15 are known to be stress and/or GC responsive and play a role in neurobiological processes including synaptic plasticity and neuronal differentiation. We found increased binding of MR and GR to GREs within Klf2, Klf9 and Klf15 in the hippocampus, amygdala, prefrontal cortex, and neocortex after acute stress and resulting from circadian variation, which was accompanied by upregulation of corresponding hnRNA and mRNA levels. Adrenalectomy abolished transcriptional upregulation of specific Klf genes. These results show that MRs and GRs regulate Klf gene expression throughout the brain following exposure to acute stress or in response to circadian variation, likely alongside other transcription factors. Elsevier 2023-03-07 /pmc/articles/PMC10024234/ /pubmed/36942087 http://dx.doi.org/10.1016/j.ynstr.2023.100532 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Original Research Article Kennedy, Clare L.M. Price, Emily M. Mifsud, Karen R. Salatino, Silvia Sharma, Eshita Engledow, Simon Broxholme, John Goss, Hannah M. Reul, Johannes M.H.M. Genomic regulation of Krüppel-like-factor family members by corticosteroid receptors in the rat brain |
title | Genomic regulation of Krüppel-like-factor family members by corticosteroid receptors in the rat brain |
title_full | Genomic regulation of Krüppel-like-factor family members by corticosteroid receptors in the rat brain |
title_fullStr | Genomic regulation of Krüppel-like-factor family members by corticosteroid receptors in the rat brain |
title_full_unstemmed | Genomic regulation of Krüppel-like-factor family members by corticosteroid receptors in the rat brain |
title_short | Genomic regulation of Krüppel-like-factor family members by corticosteroid receptors in the rat brain |
title_sort | genomic regulation of krüppel-like-factor family members by corticosteroid receptors in the rat brain |
topic | Original Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10024234/ https://www.ncbi.nlm.nih.gov/pubmed/36942087 http://dx.doi.org/10.1016/j.ynstr.2023.100532 |
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