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From: Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal
Cortex of Subjects With Schizophrenia
Arch Gen Psychiatry. 2005;62(8):829-840. doi:10.1001/archpsyc.62.8.829
Figure Legend:
Study design.
Date of download: 8/3/2017
From: Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal
Cortex of Subjects With Schizophrenia
Arch Gen Psychiatry. 2005;62(8):829-840. doi:10.1001/archpsyc.62.8.829
Figure Legend:
The 6 site-specific covalent modifications at the N-terminal tails of histones H3 and H4 studied in the postmortem cohorts. Ac
indicates acetylation; Me, methylation; P, phosphorylation; single-letter amino acid codes: K, lysine; S, serine. H3meR17 is histone
H3 methylated at arginine 17; H3pS10-acK14 is a dimodified histone, defined by phosphorylation of serine 10 and acetylation of
lysine 14. H3acK9/14 is defined by the acetylation of lysines 9 and 14 on histone H3. H3meK4 is defined by the methylation of H3lysine 4. H4acK8 is defined by the acetylation of H4-lysine 8. H4acK12 is defined by the acetylation of H4-lysine 12.
Date of download: 8/3/2017
From: Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal
Cortex of Subjects With Schizophrenia
Arch Gen Psychiatry. 2005;62(8):829-840. doi:10.1001/archpsyc.62.8.829
Figure Legend:
Histone profile of the human prefrontal cortex. Representative examples of histone immunoblots for matched schizophrenia (S) and
control (C) pairs 4, 6, and 8. Note the robust immunoreactivity for each of the 6 histone modifications. Note the increased levels of
H3meR17 in S8 compared with C8. The approximate sizes of the immunoreactive bands are as follows: H3, 14.5 kDa; and H4, 10.5
kDa.
Date of download: 8/3/2017
From: Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal
Cortex of Subjects With Schizophrenia
Arch Gen Psychiatry. 2005;62(8):829-840. doi:10.1001/archpsyc.62.8.829
Figure Legend:
Laminar and cellular distribution of histone immunoreactivity in the postmortem prefrontal cortex. A and B, Sections through the full
thickness of the prefrontal cortex stained for Nissl (A) and H3meR17 (B) immunoreactivity. Notice in (B) the punctate staining pattern
in cortical layers I through VI but the very weak labeling in white matter (WM). C-L, Digitized images from prefrontal layer III of
control 4 (C, E, G, I, and K) and matched subject with schizophrenia 4 (D, F, H, J, and L) stained for Nissl (C and D), H3meR17 (E
and F), H3pS10-acK14 (G and H), and H4acK12 (I and J) immunoreactivity. Two sections (K and L) were processed without primary
Date
of download:
8/3/2017
antibody.
Notice the
robust histone immunoreactivity in the nuclei. The images were taken at the following magnifications: 2.5 × 10
(A and B) and 40 × 10 (C-L).
From: Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal
Cortex of Subjects With Schizophrenia
Arch Gen Psychiatry. 2005;62(8):829-840. doi:10.1001/archpsyc.62.8.829
Figure Legend:
Mean levels of histone immunoreactivity (A) and metabolic gene transcripts (B) in 21 subjects with schizophrenia and 21 matched
controls. Metabolic gene transcripts (B) are shown after internal normalization to β-actin and log-transformation. There are no
statistically significant differences between the 2 cohorts. Error bars indicate standard error of the mean.
Date of download: 8/3/2017
From: Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal
Cortex of Subjects With Schizophrenia
Arch Gen Psychiatry. 2005;62(8):829-840. doi:10.1001/archpsyc.62.8.829
Figure Legend:
Metabolic gene transcripts in the prefrontal cortex. Digitized images from film autoradiograms of complementary DNA (cDNA)
arrays. Representative examples of hybridization signals for 6 genes on the cDNA arrays. Note the intense signal for the gene
expressed at high levels (GAPDH) and the lower-intensity signals for the remaining metabolic cDNAs (CRYM, HPRT, OAZ1, PDK2,
and UCHL1) (magnification ×1).
Date of download: 8/3/2017
From: Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal
Cortex of Subjects With Schizophrenia
Arch Gen Psychiatry. 2005;62(8):829-840. doi:10.1001/archpsyc.62.8.829
Figure Legend:
Decreased metabolic gene expression in the prefrontal cortex of subjects with schizophrenia is associated with high levels of
H3meR17. A, For each of the 41 matched pairs, relative levels of H3meR17 and levels of metabolic gene transcripts. Dotted vertical
line indicates an H3meR17 level of 1.3, the cutoff point for subjects with schizophrenia with H3meR17 levels of 1.3 or greater
relative to matched controls (Schiz-H3meR17≥1.3C). The dashed horizontal line indicates zero difference in gene expression between
subjects with schizophrenia and controls. Note that the Schiz-H3meR17≥1.3C subgroup (n = 8) lacks subjects with high levels of gene
Date
of download:
8/3/2017
expression.
B, Mean
levels of metabolic gene transcripts in subjects with schizophrenia relative to matched controls. Subjects with
schizophrenia (n = 41) were divided into the Schiz-H3meR17≥1.3C subgroup (n = 8) and a subgroup with H3meR17 levels of less
From: Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal
Cortex of Subjects With Schizophrenia
Arch Gen Psychiatry. 2005;62(8):829-840. doi:10.1001/archpsyc.62.8.829
Figure Legend:
Long-term antipsychotic drug treatment does not affect H3 methylation and phosphoacetylation in whole chromatin of the rodent
prefrontal cortex. A, Western blot from acid-extracted proteins from the rostral medial cortex of mice treated for 14 days with
haloperidol or risperidone. Immunoreactivity for H3pS10-acK14, H3meR17, and H4acK12 in drug-treated animals is comparable to
that in their saline-treated littermates. B, Quantitative results for H3pS10-acK14 and H3meR17 immunoreactivity in the rostral
medial cortex. Levels in haloperidol- and risperidone-treated animals were normalized to the levels in their saline-treated littermates.
Date
download:
8/3/2017
Note of
that
differences
between drug- and saline-treated animals are less than 15%. Error bars represent standard error of the mean.
From: Chromatin Alterations Associated With Down-regulated Metabolic Gene Expression in the Prefrontal
Cortex of Subjects With Schizophrenia
Arch Gen Psychiatry. 2005;62(8):829-840. doi:10.1001/archpsyc.62.8.829
Figure Legend:
Subgroup model for prefrontal cortex (PFC) hypometabolism in schizophrenia. Of all subjects diagnosed as having schizophrenia,
only a portion show down-regulated metabolic gene expression in the PFC. This hypothesis is indirectly supported by findings from
in vivo imaging studies because the severity of prefrontal hypoactivity and hypometabolism shows considerable variability among
subjects diagnosed as having schizophrenia. Among schizophrenic subjects with PFC hypometabolism/down-regulated metabolic
gene expression, there is a subgroup that shows high levels of open chromatin-associated H3 methylation, H3meR17. Alterations in
Date
download:
8/3/2017 including H3 phosphoacetylation, H3pS10-acK14, may also be associated with prefrontal
otherofhistone
modifications,
hypometabolism and dysregulated metabolic gene transcription. Ac indicates acetylation; H3, histone H3; K, lysine; Me, methylation;