Distinct regulation of hippocampal neuroplasticity and ciliary genes by corticosteroid receptors

Karen R. Mifsud, Clare L. M. Kennedy, Silvia Salatino, Eshita Sharma, Emily M. Price, Samantha N. Haque, Andriana Gialeli, Hannah M. Goss, Polina E. Panchenko, John Broxholme, Simon Engledow, Helen Lockstone, Oscar Cordero Llana and Johannes M. H. M. Reul ()
Additional contact information
Karen R. Mifsud: University of Bristol
Clare L. M. Kennedy: University of Bristol
Silvia Salatino: University of Oxford
Eshita Sharma: University of Oxford
Emily M. Price: University of Bristol
Samantha N. Haque: University of Bristol
Andriana Gialeli: University of Bristol
Hannah M. Goss: University of Bristol
Polina E. Panchenko: University of Bristol
John Broxholme: University of Oxford
Simon Engledow: University of Oxford
Helen Lockstone: University of Oxford
Oscar Cordero Llana: University of Bristol
Johannes M. H. M. Reul: University of Bristol

Nature Communications, 2021, vol. 12, issue 1, 1-23

Abstract: Abstract Glucocorticoid hormones (GCs) — acting through hippocampal mineralocorticoid receptors (MRs) and glucocorticoid receptors (GRs) — are critical to physiological regulation and behavioural adaptation. We conducted genome-wide MR and GR ChIP-seq and Ribo-Zero RNA-seq studies on rat hippocampus to elucidate MR- and GR-regulated genes under circadian variation or acute stress. In a subset of genes, these physiological conditions resulted in enhanced MR and/or GR binding to DNA sequences and associated transcriptional changes. Binding of MR at a substantial number of sites however remained unchanged. MR and GR binding occur at overlapping as well as distinct loci. Moreover, although the GC response element (GRE) was the predominant motif, the transcription factor recognition site composition within MR and GR binding peaks show marked differences. Pathway analysis uncovered that MR and GR regulate a substantial number of genes involved in synaptic/neuro-plasticity, cell morphology and development, behavior, and neuropsychiatric disorders. We find that MR, not GR, is the predominant receptor binding to >50 ciliary genes; and that MR function is linked to neuronal differentiation and ciliogenesis in human fetal neuronal progenitor cells. These results show that hippocampal MRs and GRs constitutively and dynamically regulate genomic activities underpinning neuronal plasticity and behavioral adaptation to changing environments.

Date: 2021
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-021-24967-z Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-24967-z

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-021-24967-z

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().