title: Chromatin alterations associated with down-regulated metabolic gene expression in the prefrontal cortex of subjects with schizophrenia.
abstract: 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.
  
  
  METHODS
  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.affiliation: Brudnick Neuropsychiatric Research Institute, Department of Psychiatry and Bioinformatics Unit, Information Services, University of Massachusetts Medical School, Worcester, MA 01604, USA. Schahram.akbarian@umassmed.edu
authors.forename: Schahram
authors.initials: S
authors.lastname: Akbarian
authors.forename: Martin G
authors.initials: MG
authors.lastname: Ruehl
authors.forename: Erin
authors.initials: E
authors.lastname: Bliven
authors.forename: Lori A
authors.initials: LA
authors.lastname: Luiz
authors.forename: Amy C
authors.initials: AC
authors.lastname: Peranelli
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Baker
authors.forename: Rosalinda C
authors.initials: RC
authors.lastname: Roberts
authors.forename: William E
authors.initials: WE
authors.lastname: Bunney
authors.forename: Robert C
authors.initials: RC
authors.lastname: Conley
authors.forename: Edward G
authors.initials: EG
authors.lastname: Jones
authors.forename: Carol A
authors.initials: CA
authors.lastname: Tamminga
authors.forename: Yin
authors.initials: Y
authors.lastname: Guo
mesh_terms: D002843:Chromatin / Q000235:genetics* / Q000378:metabolism; D015536:Down-Regulation; D044127:Epigenesis, Genetic / Q000235:genetics; D015870:Gene Expression / Q000235:genetics*; D020869:Gene Expression Profiling; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D020411:Oligonucleotide Array Sequence Analysis; D017397:Prefrontal Cortex / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012559:Schizophrenia / Q000235:genetics* / Q000378:metabolism
chemical_list: D002843:Chromatin; D006657:Histones