Histone deacetylase inhibitors and candidate gene expression: An in vivo and in vitro approach to studying chromatin remodeling in a clinical population

Gavin, David P.; Kartan, Saritha; Chase, Kayla A.; Jayaraman, Sundararajan; Sharma, Rajiv P.

doi:10.1016/j.jpsychires.2008.12.006

Cited by 76 publications

(72 citation statements)

References 34 publications

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“…ChIP and MeDIP experiments were conducted using a previously published protocol (Gavin et al, 2009a;Dong et al, 2008). We used rabbit anti-GADD45b polyclonal antibody (Aviva, ARP48346_P050).…”

Section: Gadd45b Chromatin Immunoprecipitation (Chip) and Methylated mentioning

confidence: 99%

Growth Arrest and DNA-Damage-Inducible, Beta (GADD45b)-Mediated DNA Demethylation in Major Psychosis

Gavin

Sharma

Chase

et al. 2011

Neuropsychopharmacol

102

119

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Aberrant neocortical DNA methylation has been suggested to be a pathophysiological contributor to psychotic disorders. Recently, a growth arrest and DNA-damage-inducible, beta (GADD45b) protein-coordinated DNA demethylation pathway, utilizing cytidine deaminases and thymidine glycosylases, has been identified in the brain. We measured expression of several members of this pathway in parietal cortical samples from the Stanley Foundation Neuropathology Consortium (SFNC) cohort. We find an increase in GADD45b mRNA and protein in patients with psychosis. In immunohistochemistry experiments using samples from the Harvard Brain Tissue Resource Center, we report an increased number of GADD45b-stained cells in prefrontal cortical layers II, III, and V in psychotic patients. Brain-derived neurotrophic factor IX (BDNF IXabcd) was selected as a readout gene to determine the effects of GADD45b expression and promoter binding. We find that there is less GADD45b binding to the BDNF IXabcd promoter in psychotic subjects. Further, there is reduced BDNF IXabcd mRNA expression, and an increase in 5-methylcytosine and 5-hydroxymethylcytosine at its promoter. On the basis of these results, we conclude that GADD45b may be increased in psychosis compensatory to its inability to access gene promoter regions.

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Section: Gadd45b Chromatin Immunoprecipitation (Chip) and Methylated mentioning

confidence: 99%

Growth Arrest and DNA-Damage-Inducible, Beta (GADD45b)-Mediated DNA Demethylation in Major Psychosis

Gavin

Sharma

Chase

et al. 2011

Neuropsychopharmacol

102

119

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“…Other potential mechanisms might be related to a synergistic increased dopamine or acetylcholine release in the medial prefrontal cortex (Ichikawa et al, 2005;Huang et al, 2006). Recently, valproate is implicated in chromatin remodelling through GABAergic mechanisms (Gavin et al, 2009), and may exert differential effects under the influence of antipsychotics (Dong et al, 2008).…”

Section: Discussionmentioning

confidence: 99%

Augmentation of atypical antipsychotics with valproic acid. An open‐label study for most difficult patients with schizophrenia

Suzuki

Uchida

Takeuchi

et al. 2009

Human Psychopharmacology

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“…Furthermore, VPA promotes neuronal differentiation from progenitor stages (Hsieh et al, 2004;Yu et al, 2009) and the drug induces in cell culture and brain the upregulation of open chromatinassociated histone acetylation and methylation markings at promoters of genes with a key role in neurotransmission (Gavin et al, 2009;Guidotti et al, 2009;Huang et al, 2007b). It will be interesting to quantify these VPA-dependent effects on pluripotency and neuronal differentiation, and to compare VPA treatment responders to non-responders.…”

Section: Psychiatric Epigenetics In the Culture Dish?mentioning

confidence: 99%

Epigenetics in the Human Brain

Houston

Peter

Mitchell

et al. 2012

Neuropsychopharmacol

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Many cellular constituents in the human brain permanently exit from the cell cycle during pre-or early postnatal development, but little is known about epigenetic regulation of neuronal and glial epigenomes during maturation and aging, including changes in mood and psychosis spectrum disorders and other cognitive or emotional disease. Here, we summarize the current knowledge base as it pertains to genome organization in the human brain, including the regulation of DNA cytosine methylation and hydroxymethylation, and a subset of (altogether 4100) residue-specific histone modifications associated with gene expression, and silencing and various other functional chromatin states. We propose that high-resolution mapping of epigenetic markings in postmortem brain tissue or neural cultures derived from induced pluripotent cells (iPS), in conjunction with transcriptome profiling and whole-genome sequencing, will increasingly be used to define the molecular pathology of specific cases diagnosed with depression, schizophrenia, autism, or other major psychiatric disease. We predict that these highly integrative explorations of genome organization and function will provide an important alternative to conventional approaches in human brain studies, which mainly are aimed at uncovering group effects by diagnosis but generally face limitations because of cohort size.

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Histone deacetylase inhibitors and candidate gene expression: An in vivo and in vitro approach to studying chromatin remodeling in a clinical population

Cited by 76 publications

References 34 publications

Growth Arrest and DNA-Damage-Inducible, Beta (GADD45b)-Mediated DNA Demethylation in Major Psychosis

Growth Arrest and DNA-Damage-Inducible, Beta (GADD45b)-Mediated DNA Demethylation in Major Psychosis

Augmentation of atypical antipsychotics with valproic acid. An open‐label study for most difficult patients with schizophrenia

Epigenetics in the Human Brain

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