title: A seasonal switch in histone deacetylase gene expression in the hypothalamus and their capacity to modulate nuclear signaling pathways.
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.
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
authors.forename: Patrick N
authors.initials: PN
authors.lastname: Stoney
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
authors.forename: Diana
authors.initials: D
authors.lastname: Rodrigues
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, Scotland, UK; Faculty of Life Sciences, University of Bradford, Richmond Road, Bradford BD7 1DP, UK.
authors.forename: Gisela
authors.initials: G
authors.lastname: Helfer
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
authors.forename: Thabat
authors.initials: T
authors.lastname: Khatib
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Ashton
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Hay
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Starr
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK.
authors.forename: Dagmara
authors.initials: D
authors.lastname: Kociszewska
authors.affiliation: Rowett Institute of Nutrition and Health, University of Aberdeen, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, Scotland, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Morgan
authors.affiliation: Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen AB25 2ZD, Scotland, UK. Electronic address: p.j.mccaffery@abdn.ac.uk.
authors.forename: Peter
authors.initials: P
authors.lastname: McCaffery
mesh_terms: D000818:Animals; D002460:Cell Line; D063928:Ependymoglial Cells / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D006655:Histone Deacetylases / Q000235:genetics* / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects / Q000378:metabolism*; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D017440:Photoperiod; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012621:Seasons; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D006655:Histone Deacetylases
keywords: Histone deacetylase; Inflammatory; Lipopolysaccharide; Nucleus; Tumour necrosis factor alpha