Epigenetic Suppression of Mouse Per2 Expression in the Suprachiasmatic Nucleus by the Inhalational Anesthetic, Sevoflurane
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{"title"=>"Epigenetic suppression of mouse Per2 expression in the suprachiasmatic nucleus by the inhalational anesthetic, sevoflurane", "type"=>"journal", "authors"=>[{"first_name"=>"Keisuke", "last_name"=>"Mori", "scopus_author_id"=>"55629767300"}, {"first_name"=>"Norio", "last_name"=>"Iijima", "scopus_author_id"=>"55295945400"}, {"first_name"=>"Shimpei", "last_name"=>"Higo", "scopus_author_id"=>"24337976200"}, {"first_name"=>"Satoko", "last_name"=>"Aikawa", "scopus_author_id"=>"56154407100"}, {"first_name"=>"Izumi", "last_name"=>"Matsuo", "scopus_author_id"=>"55630654600"}, {"first_name"=>"Ken", "last_name"=>"Takumi", "scopus_author_id"=>"9038775900"}, {"first_name"=>"Atsuhiro", "last_name"=>"Sakamoto", "scopus_author_id"=>"7201516353"}, {"first_name"=>"Hitoshi", "last_name"=>"Ozawa", "scopus_author_id"=>"7202195724"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"pmid"=>"24498074", "sgr"=>"84900339848", "doi"=>"10.1371/journal.pone.0087319", "scopus"=>"2-s2.0-84900339848", "pui"=>"373059512", "issn"=>"19326203"}, "id"=>"c4fcc2b0-023a-3244-90bc-b20fc8d9dfec", "abstract"=>"BACKGROUND: We previously reported that sevoflurane anesthesia reversibly suppresses the expression of the clock gene, Period2 (Per2), in the mouse suprachiasmatic nucleus (SCN). However, the molecular mechanisms underlying this suppression remain unclear. In this study, we examined the possibility that sevoflurane suppresses Per2 expression via epigenetic modification of the Per2 promoter.\\n\\nMETHODS: Mice were anesthetized with a gas mixture of 2.5% sevoflurane/40% oxygen at a 6 L/min flow for 1 or 4 h. After termination, brains were removed and samples of SCN tissue were derived from frozen brain sections. Chromatin immunoprecipitation (ChIP) assays using anti-acetylated-histone antibodies were performed to investigate the effects of sevoflurane on histone acetylation of the Per2 promoter. Interaction between the E'-box (a cis-element in the Per2 promoter) and CLOCK (the Clock gene product) was also assessed by a ChIP assay using an anti-CLOCK antibody. The SCN concentration of nicotinamide adenine dinucleotide (NAD(+)), a CLOCK regulator, was assessed by liquid chromatography-mass spectrometry.\\n\\nRESULTS: Acetylation of histone H4 in the proximal region of the Per2 promoter was significantly reduced by sevoflurane. This change in the epigenetic profile of the Per2 gene was observed prior to suppression of Per2 expression. Simultaneously, a reduction in the CLOCK-E'-box interaction in the Per2 promoter was observed. Sevoflurane treatment did not affect the concentration of NAD(+) in the SCN.\\n\\nCONCLUSIONS: Independent of NAD(+) concentration in the SCN, sevoflurane decreases CLOCK binding to the Per2 promoter E'-box motif, reducing histone acetylation and leading to suppression of Per2 expression.", "link"=>"http://www.mendeley.com/research/epigenetic-suppression-mouse-per2-expression-suprachiasmatic-nucleus-inhalational-anesthetic-sevoflu", "reader_count"=>24, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Librarian"=>1, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Librarian"=>1, "Student > Doctoral Student"=>2, "Researcher"=>4, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Student > Master"=>4, "Other"=>1, "Student > Bachelor"=>2, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>7, "Medicine and Dentistry"=>8, "Agricultural and Biological Sciences"=>5, "Veterinary Science and Veterinary Medicine"=>1, "Psychology"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>8}, "Psychology"=>{"Psychology"=>1}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>7}, "Unspecified"=>{"Unspecified"=>2}, "Veterinary Science and Veterinary Medicine"=>{"Veterinary Science and Veterinary Medicine"=>1}}, "reader_count_by_country"=>{"Canada"=>1, "Japan"=>1, "United Kingdom"=>1}, "group_count"=>2}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1371172"], "description"=>"<p>The light/dark condition, sampling periods, and time of anesthetic treatment (gray bar) are illustrated in the upper scheme. Arrowheads indicate the time of sampling. Representative PCR results are shown in the middle panel. CLOCK-E’-box binding in each sample is shown in the lower graph. Data are mean ± SEM. * denotes a statistically significant difference between control and anesthetic treatment (Student’s t-test; <i>p</i><0.05).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "Chronobiology", "genetics", "epigenetics", "Histone modification", "gene expression", "Molecular cell biology", "neuroscience", "anesthesiology", "Anesthetic mechanisms", "binding", "promoter", "sevoflurane"], "article_id"=>922033, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Keisuke Mori", "Norio Iijima", "Shimpei Higo", "Satoko Aikawa", "Izumi Matsuo", "Ken Takumi", "Atsuhiro Sakamoto", "Hitoshi Ozawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087319.g004", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Suppression_of_CLOCK_binding_to_the_E_box_in_the_Per2_promoter_region_under_sevoflurane_anesthesia_/922033", "title"=>"Suppression of CLOCK binding to the E’-box in the <i>Per2</i> promoter region under sevoflurane anesthesia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 03:07:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1371170"], "description"=>"<p>(A) Diagram of CpG island around the <i>Per2</i> locus. CpG sites are numbered and indicated by upward arrowheads. Arrows indicate pairs of methylation-specific primers used to amplify the region of the CpG island containing the E’-box. (B) Methylation rate of 10 individual sites in the <i>Per2</i> promoter and four CpG sites in exon 1.</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "Chronobiology", "genetics", "epigenetics", "Histone modification", "gene expression", "Molecular cell biology", "neuroscience", "anesthesiology", "Anesthetic mechanisms", "methylation", "promoter", "sevoflurane"], "article_id"=>922031, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Keisuke Mori", "Norio Iijima", "Shimpei Higo", "Satoko Aikawa", "Izumi Matsuo", "Ken Takumi", "Atsuhiro Sakamoto", "Hitoshi Ozawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087319.g002", "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_DNA_methylation_profile_of_the_Per2_promoter_region_following_sevoflurane_anesthesia_/922031", "title"=>"DNA methylation profile of the <i>Per2</i> promoter region following sevoflurane anesthesia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 03:07:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1371171"], "description"=>"<p>(A) Schematic representation of the light/dark condition, sampling periods, and time of anesthetic treatment (gray bar). Arrowheads indicate the time of sampling. (B) Schematic representation of <i>Per2</i> promoter. The positions of primer pairs used for PCR are indicated by arrows. (C, D) Representative PCR results and acetylation levels of histone H3 or H4 at the proximal (C) or distal (D) regions of the <i>Per2</i> promoter. Data are mean ± SEM. * denotes a statistically significant difference between control and anesthetic treatment. † denotes a statistically significant difference between the different time periods of anesthetic exposure (two-way ANOVA followed by Bonferroni test; <i>p</i><0.05).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "Chronobiology", "genetics", "epigenetics", "Histone modification", "gene expression", "Molecular cell biology", "neuroscience", "anesthesiology", "Anesthetic mechanisms", "histone", "acetylation", "cre", "promoter", "sevoflurane"], "article_id"=>922032, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Keisuke Mori", "Norio Iijima", "Shimpei Higo", "Satoko Aikawa", "Izumi Matsuo", "Ken Takumi", "Atsuhiro Sakamoto", "Hitoshi Ozawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087319.g003", "stats"=>{"downloads"=>0, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Changes_in_histone_acetylation_at_CRE_and_E_box_in_the_Per2_promoter_under_sevoflurane_anesthesia_/922032", "title"=>"Changes in histone acetylation at CRE and E’-box in the <i>Per2</i> promoter under sevoflurane anesthesia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 03:07:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1371169"], "description"=>"<p>(A) The light/dark conditions and sampling periods are illustrated in the upper scheme. White and black bars indicate light and dark periods, respectively. Arrowheads indicate the time of sampling. Lower graph shows the quantitative diurnal change in <i>Per2</i> expression. (B) The light/dark condition, sampling periods, and time of anesthetic treatment (gray bar) are illustrated in the upper scheme. Changes in <i>Per2</i> expression under anesthetic treatment are shown in the lower graph. Data are mean ± SEM. * denotes a statistically significant difference between anesthetic treatment and control (two-way ANOVA; <i>p</i><0.05).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "Chronobiology", "genetics", "epigenetics", "Histone modification", "gene expression", "Molecular cell biology", "neuroscience", "anesthesiology", "Anesthetic mechanisms", "scn", "sevoflurane"], "article_id"=>922030, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Keisuke Mori", "Norio Iijima", "Shimpei Higo", "Satoko Aikawa", "Izumi Matsuo", "Ken Takumi", "Atsuhiro Sakamoto", "Hitoshi Ozawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087319.g001", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Inhibition_of_Per2_expression_in_the_SCN_under_sevoflurane_anesthesia_/922030", "title"=>"Inhibition of <i>Per2</i> expression in the SCN under sevoflurane anesthesia.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 03:07:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1371179", "https://ndownloader.figshare.com/files/1371180", "https://ndownloader.figshare.com/files/1371181", "https://ndownloader.figshare.com/files/1371182"], "description"=>"<div><p>Background</p><p>We previously reported that sevoflurane anesthesia reversibly suppresses the expression of the clock gene, <i>Period2</i> (<i>Per2</i>), in the mouse suprachiasmatic nucleus (SCN). However, the molecular mechanisms underlying this suppression remain unclear. In this study, we examined the possibility that sevoflurane suppresses <i>Per2</i> expression <i>via</i> epigenetic modification of the <i>Per2</i> promoter.</p><p>Methods</p><p>Mice were anesthetized with a gas mixture of 2.5% sevoflurane/40% oxygen at a 6 L/min flow for 1 or 4 h. After termination, brains were removed and samples of SCN tissue were derived from frozen brain sections. Chromatin immunoprecipitation (ChIP) assays using anti-acetylated-histone antibodies were performed to investigate the effects of sevoflurane on histone acetylation of the <i>Per2</i> promoter. Interaction between the E’-box (a cis-element in the <i>Per2</i> promoter) and CLOCK (the <i>Clock</i> gene product) was also assessed by a ChIP assay using an anti-CLOCK antibody. The SCN concentration of nicotinamide adenine dinucleotide (NAD<sup>+</sup>), a CLOCK regulator, was assessed by liquid chromatography-mass spectrometry.</p><p>Results</p><p>Acetylation of histone H4 in the proximal region of the <i>Per2</i> promoter was significantly reduced by sevoflurane. This change in the epigenetic profile of the <i>Per2</i> gene was observed prior to suppression of <i>Per2</i> expression. Simultaneously, a reduction in the CLOCK-E’-box interaction in the <i>Per2</i> promoter was observed. Sevoflurane treatment did not affect the concentration of NAD<sup>+</sup> in the SCN.</p><p>Conclusions</p><p>Independent of NAD<sup>+</sup> concentration in the SCN, sevoflurane decreases CLOCK binding to the <i>Per2</i> promoter E’-box motif, reducing histone acetylation and leading to suppression of <i>Per2</i> expression.</p></div>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "Chronobiology", "genetics", "epigenetics", "Histone modification", "gene expression", "Molecular cell biology", "neuroscience", "anesthesiology", "Anesthetic mechanisms", "epigenetic", "suppression", "suprachiasmatic", "nucleus", "inhalational", "sevoflurane"], "article_id"=>922040, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Keisuke Mori", "Norio Iijima", "Shimpei Higo", "Satoko Aikawa", "Izumi Matsuo", "Ken Takumi", "Atsuhiro Sakamoto", "Hitoshi Ozawa"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0087319.s001", "https://dx.doi.org/10.1371/journal.pone.0087319.s002", "https://dx.doi.org/10.1371/journal.pone.0087319.s003", "https://dx.doi.org/10.1371/journal.pone.0087319.s004"], "stats"=>{"downloads"=>0, "page_views"=>7, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Epigenetic_Suppression_of_Mouse_Per2_Expression_in_the_Suprachiasmatic_Nucleus_by_the_Inhalational_Anesthetic_Sevoflurane/922040", "title"=>"Epigenetic Suppression of Mouse <i>Per2</i> Expression in the Suprachiasmatic Nucleus by the Inhalational Anesthetic, Sevoflurane", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-01-31 03:07:46"}
  • {"files"=>["https://ndownloader.figshare.com/files/1371174"], "description"=>"<p>Data were normalized using estimations of the total protein in each sample, and are shown as mean ± SEM (Student’s t-test; <i>p</i><0.05).</p>", "links"=>[], "tags"=>["Anatomy and physiology", "Physiological processes", "Chronobiology", "genetics", "epigenetics", "Histone modification", "gene expression", "Molecular cell biology", "neuroscience", "anesthesiology", "Anesthetic mechanisms", "sevoflurane", "nam"], "article_id"=>922035, "categories"=>["Biological Sciences", "Medicine"], "users"=>["Keisuke Mori", "Norio Iijima", "Shimpei Higo", "Satoko Aikawa", "Izumi Matsuo", "Ken Takumi", "Atsuhiro Sakamoto", "Hitoshi Ozawa"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0087319.g005", "stats"=>{"downloads"=>0, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Effects_of_sevoflurane_treatment_on_NAD_NMN_and_NAM_levels_in_the_SCN_/922035", "title"=>"Effects of sevoflurane treatment on NAD+, NMN, and NAM levels in the SCN.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-01-31 03:07:46"}

PMC Usage Stats | Further Information

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Relative Metric

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