Journal article

Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal Cortex of Subjects With Schizophrenia


Authors listAkbarian, S; Rühl, M; Bliven, E; Luiz, LA; Peranelli, AC; Baker, SP; Roberts, RC; Burnicy, WE; Conley, RC; Jones, EG; Tamminga, CA; Guo, Y

Publication year2005

Pages829-840

JournalArchives of General Psychiatry

Volume number62

Issue number8

DOI Linkhttps://doi.org/10.1001/archpsyc.62.8.829

PublisherAMA American Medical Association


Abstract

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.
To test the hypothesis that down-regulated metabolic gene expression is
associated with histone modification changes in the prefrontal cortex of
subjects with schizophrenia.
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.
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.
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.




Citation Styles

Harvard Citation styleAkbarian, S., Rühl, M., Bliven, E., Luiz, L., Peranelli, A., Baker, S., et al. (2005) Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal Cortex of Subjects With Schizophrenia, Archives of General Psychiatry, 62(8), pp. 829-840. https://doi.org/10.1001/archpsyc.62.8.829

APA Citation styleAkbarian, S., Rühl, M., Bliven, E., Luiz, L., Peranelli, A., Baker, S., Roberts, R., Burnicy, W., Conley, R., Jones, E., Tamminga, C., & Guo, Y. (2005). Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal Cortex of Subjects With Schizophrenia. Archives of General Psychiatry. 62(8), 829-840. https://doi.org/10.1001/archpsyc.62.8.829


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