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    A seasonal switch in histone deacetylase gene expression in the hypothalamus and their capacity to modulate nuclear signaling pathways

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    Publication date
    2016
    Author
    Stoney, P.N.
    Rodrigues, D.
    Helfer, Gisela
    Khatib, T.
    Ashton, A.
    Hay, E.A.
    Starr, R.
    Kociszewska, D.
    Morgan, P.J.
    McCaffery, P.J.
    Keyword
    Histone deacetylases (HDACs); Gene expression; Hypothalamus; Inflammatory; Animals; Seasonal changes pathways; Nuclear receptor pathways
    Rights
    © 2016 The Authors. Published open access by Elsevier under a Creative Commons license, Attribution 4.0 International (CC BY 4.0).
    Peer-Reviewed
    Yes
    
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    Abstract
    Seasonal animals undergo changes in physiology and behavior between summer and winter conditions. These changes are in part driven by a switch in a series of hypothalamic genes under transcriptional control by hormones and, of recent interest, inflammatory factors. Crucial to the control of transcription are histone deacetylases (HDACs), generally acting to repress transcription by local histone modification. Seasonal changes in hypothalamic HDAC transcripts were investigated in photoperiod-sensitive F344 rats by altering the day-length (photoperiod). HDAC4, 6 and 9 were found to change in expression. The potential influence of HDACs on two hypothalamic signaling pathways that regulate transcription, inflammatory and nuclear receptor signaling, was investigated. For inflammatory signaling the focus was on NF-κB because of the novel finding made that its expression is seasonally regulated in the rat hypothalamus. For nuclear receptor signaling it was discovered that expression of retinoic acid receptor beta was regulated seasonally. HDAC modulation of NF-κB-induced pathways was examined in a hypothalamic neuronal cell line and primary hypothalamic tanycytes. HDAC4/5/6 inhibition altered the control of gene expression (Fos, Prkca, Prkcd and Ptp1b) by inducers of NF-κB that activate inflammation. These inhibitors also modified the action of nuclear receptor ligands thyroid hormone and retinoic acid. Thus seasonal changes in HDAC4 and 6 have the potential to epigenetically modify multiple gene regulatory pathways in the hypothalamus that could act to limit inflammatory pathways in the hypothalamus during long-day summer-like conditions.
    URI
    http://hdl.handle.net/10454/11081
    Version
    Published version
    Citation
    Stoney PN, Rodrigues D, Helfer G et al(2016) A seasonal switch in histone deacetylase gene expression in the hypothalamus and their capacity to modulate nuclear signaling pathways. Brain, Behavior, and Immunity. 61: 340-352.
    Link to publisher’s version
    http://dx.doi.org/10.1016/j.bbi.2016.12.013
    Type
    Article
    Collections
    Life Sciences Publications

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