Chromatin alterations associated with down-regulated metabolic gene expression in the prefrontal cortex of subjects with schizophrenia

Schahram Akbarian, Martin G. Ruehl, Erin Bliven, Lori A. Luiz, Amy C. Peranelli, Stephen P. Baker, Rosalinda C. Roberts, William E. Bunney, Robert C. Conley, Edward G. Jones, Carol A. Tamminga, Yin Guo

Research output: Contribution to journalArticle

93 Citations (Scopus)

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. 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.

Original languageEnglish (US)
Pages (from-to)829-840
Number of pages12
JournalArchives of General Psychiatry
Volume62
Issue number8
DOIs
StatePublished - Aug 2005

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Prefrontal Cortex
Chromatin
Schizophrenia
Histone Code
Gene Expression
Histones
Arginine
Regulator Genes
Acetylation
Oligonucleotide Array Sequence Analysis
Reverse Transcriptase Polymerase Chain Reaction
Transcriptome
Immunoblotting
Epigenomics
Serine
Methylation
Genes
Lysine
Real-Time Polymerase Chain Reaction
Complementary DNA

ASJC Scopus subject areas

  • Psychiatry and Mental health

Cite this

Chromatin alterations associated with down-regulated metabolic gene expression in the prefrontal cortex of subjects with schizophrenia. / Akbarian, Schahram; Ruehl, Martin G.; Bliven, Erin; Luiz, Lori A.; Peranelli, Amy C.; Baker, Stephen P.; Roberts, Rosalinda C.; Bunney, William E.; Conley, Robert C.; Jones, Edward G.; Tamminga, Carol A.; Guo, Yin.

In: Archives of General Psychiatry, Vol. 62, No. 8, 08.2005, p. 829-840.

Research output: Contribution to journalArticle

Akbarian, S, Ruehl, MG, Bliven, E, Luiz, LA, Peranelli, AC, Baker, SP, Roberts, RC, Bunney, WE, Conley, RC, Jones, EG, Tamminga, CA & Guo, Y 2005, 'Chromatin alterations associated with down-regulated metabolic gene expression in the prefrontal cortex of subjects with schizophrenia', Archives of General Psychiatry, vol. 62, no. 8, pp. 829-840. https://doi.org/10.1001/archpsyc.62.8.829
Akbarian, Schahram ; Ruehl, Martin G. ; Bliven, Erin ; Luiz, Lori A. ; Peranelli, Amy C. ; Baker, Stephen P. ; Roberts, Rosalinda C. ; Bunney, William E. ; Conley, Robert C. ; Jones, Edward G. ; Tamminga, Carol A. ; Guo, Yin. / Chromatin alterations associated with down-regulated metabolic gene expression in the prefrontal cortex of subjects with schizophrenia. In: Archives of General Psychiatry. 2005 ; Vol. 62, No. 8. pp. 829-840.
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