BACKGROUND: Schizophrenia is frequently accompanied by hypometabolism and altered gene expression in the prefrontal cortex. Cellular metabolism regulates chromatin structure, including covalent histone modifications, which are epigenetic regulators of gene expression. OBJECTIVE: To test the hypothesis that down-regulated metabolic gene expression is associated with histone modification changes in the prefrontal cortex of subjects with schizophrenia. DESIGN AND SUBJECTS: Histones and gene transcripts were profiled in the postmortem prefrontal cortex of 41 subjects with schizophrenia and 41 matched controls. The phosphorylation, acetylation, and methylation of 6 lysine, serine, and arginine residues of histones H3 and H4 were examined together with 16 metabolic gene transcripts using serial immunoblotting, immunohistochemical analysis, custom-made complementary DNA arrays, and quantitative real-time reverse transcriptase-polymerase chain reaction. RESULTS: Subjects with schizophrenia, as a group, showed no significant alterations in histone profiles or gene expression. In a subgroup of 8 patients with schizophrenia, levels of H3-(methyl)arginine 17, H3meR17, exceeded control values by 30%, and this was associated with the decreased expression of 4 metabolic transcripts. CONCLUSIONS: High levels of H3-(methyl)arginine 17 are associated with down-regulated metabolic gene expression in the prefrontal cortex of a subset of subjects with schizophrenia. Histone modifications may contribute to the pathogenesis of prefrontal dysfunction in schizophrenia.
BACKGROUND:Schizophrenia is frequently accompanied by hypometabolism and altered gene expression in the prefrontal cortex. Cellular metabolism regulates chromatin structure, including covalent histone modifications, which are epigenetic regulators of gene expression. OBJECTIVE: To test the hypothesis that down-regulated metabolic gene expression is associated with histone modification changes in the prefrontal cortex of subjects with schizophrenia. DESIGN AND SUBJECTS: Histones and gene transcripts were profiled in the postmortem prefrontal cortex of 41 subjects with schizophrenia and 41 matched controls. The phosphorylation, acetylation, and methylation of 6 lysine, serine, and arginine residues of histones H3 and H4 were examined together with 16 metabolic gene transcripts using serial immunoblotting, immunohistochemical analysis, custom-made complementary DNA arrays, and quantitative real-time reverse transcriptase-polymerase chain reaction. RESULTS: Subjects with schizophrenia, as a group, showed no significant alterations in histone profiles or gene expression. In a subgroup of 8 patients with schizophrenia, levels of H3-(methyl)arginine 17, H3meR17, exceeded control values by 30%, and this was associated with the decreased expression of 4 metabolic transcripts. CONCLUSIONS: High levels of H3-(methyl)arginine 17 are associated with down-regulated metabolic gene expression in the prefrontal cortex of a subset of subjects with schizophrenia. Histone modifications may contribute to the pathogenesis of prefrontal dysfunction in schizophrenia.
Authors: Hamid Mostafavi Abdolmaleky; Kuang-Hung Cheng; Stephen V Faraone; Marsha Wilcox; Stephen J Glatt; Fangming Gao; Cassandra L Smith; Rahim Shafa; Batol Aeali; Julie Carnevale; Hongjie Pan; Panagiotis Papageorgis; Jose F Ponte; Vadivelu Sivaraman; Ming T Tsuang; Sam Thiagalingam Journal: Hum Mol Genet Date: 2006-09-19 Impact factor: 6.150
Authors: Luna Fomsgaard; Jose L Moreno; Mario de la Fuente Revenga; Tomasz Brudek; Dea Adamsen; Cristobal Rio-Alamos; Justin Saunders; Anders Bue Klein; Ignasi Oliveras; Toni Cañete; Gloria Blazquez; Adolf Tobeña; Albert Fernandez-Teruel; Javier Gonzalez-Maeso; Susana Aznar Journal: Mol Neurobiol Date: 2017-03-06 Impact factor: 5.590
Authors: David P Gavin; Cherise Rosen; Kayla Chase; Dennis R Grayson; Nguwah Tun; Rajiv P Sharma Journal: J Psychiatry Neurosci Date: 2009-05 Impact factor: 6.186