Promoter Regions, Genetic

Publication Title: 
Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology

The human potassium-chloride co-transporter 3 (KCC3, SLC12A6) is involved in cell proliferation and in electro-neutral movement of ions across the cell membrane. The gene (SLC12A6) is located on chromosome 15q14, a region that has previously shown linkage with bipolar disorder, schizophrenia, rolandic epilepsy, idiopathic generalized epilepsy, autism and attention deficit/hyperactivity disorder. Furthermore, recessively inherited mutations of SLC12A6 cause Andermann syndrome, characterized by agenesis of the corpus callosum, which is associated with peripheral neuropathy and psychoses.

Author(s): 
Moser, Dirk
Ekawardhani, Savira
Kumsta, Robert
Palmason, Haukur
Bock, Christoph
Athanassiadou, Zoi
Lesch, Klaus-Peter
Meyer, Jobst
Publication Title: 
Biological Psychiatry

BACKGROUND: Epigenetic mechanisms may be involved in the reprogramming of gene expression in response to stressful stimuli. This investigation determined whether epigenetic phenomena might similarly be associated with suicide/depression. METHODS: The expression of DNA methyltransferase (DNMT) mRNA was assessed in several brain regions of individuals who had committed suicide and had been diagnosed with major depression relative to that of individuals who had died suddenly as a result of factors other than suicide.

Author(s): 
Poulter, Michael O.
Du, Lisheng
Weaver, Ian C. G.
Palkovits, MiklÛs
Faludi, G·bor
Merali, Zul
Szyf, Moshe
Anisman, Hymie
Publication Title: 
Molecular Pharmacology

The epigenetic down-regulation of genes is emerging as a possible underlying mechanism of the GABAergic neuron dysfunction in schizophrenia. For example, evidence has been presented to show that the promoters associated with reelin and GAD67 are down-regulated as a consequence of DNA methyltransferase (DNMT)-mediated hypermethylation. Using neuronal progenitor cells to study this regulation, we have previously demonstrated that DNMT inhibitors coordinately increase reelin and GAD67 mRNAs.

Author(s): 
Kundakovic, Marija
Chen, Ying
Guidotti, Alessandro
Grayson, Dennis R.
Publication Title: 
Psychoneuroendocrinology

Disturbances of volume regulating peptides like vasopressin and atrial natriuretic peptide (ANP) have been described in early abstinent patients. Aim of the present study was to evaluate possible alterations of the promoter-related DNA methylation of the ANP and vasopressin precursor genes and the related mRNA-expression of these genes in early alcohol withdrawal. We analyzed blood samples of 57 healthy controls and of 111 patients suffering from alcohol dependence that were admitted for detoxification treatment.

Author(s): 
Hillemacher, Thomas
Frieling, Helge
Luber, Katja
Yazici, Ayfer
Muschler, Marc A. N.
Lenz, Bernd
Wilhelm, Julia
Kornhuber, Johannes
Bleich, Stefan
Publication Title: 
Expert Review of Neurotherapeutics

The neuronal GABAergic mechanisms that mediate the symptomatic beneficial effects elicited by a combination of antipsychotics with valproate (a histone deacetylase inhibitor) in the treatment of psychosis (expressed by schizophrenia or bipolar disorder patients) are unknown. This prompted us to investigate whether the beneficial action of this combination results from a modification of histone tail covalent esterification or is secondary to specific chromatin remodeling.

Author(s): 
Costa, Erminio
Chen, Ying
Dong, Erbo
Grayson, Dennis R.
Kundakovic, Marija
Maloku, Ekrem
Ruzicka, William
Satta, Rosalba
Veldic, Marin
Zhubi, Adrian
Guidotti, Alessandro
Publication Title: 
Archives of General Psychiatry

CONTEXT: Although most of the effort to understand the neurobiology of depressive states and suicide has focused on neuronal processes, recent studies suggest that astroglial dysfunction may play an important role. A truncated variant of the tropomyosin-related kinase B (TrkB.T1) is expressed in astrocytes, and brain-derived neurotrophic factor-TrkB signaling has been linked to mood disorders. OBJECTIVE: To test the hypothesis that TrkB.T1 expression is downregulated in suicide completers and that this downregulation is mediated by an epigenetic process.

Author(s): 
Ernst, Carl
Deleva, Vesselina
Deng, Xiaoming
Sequeira, Adolfo
Pomarenski, Amanda
Klempan, Tim
Ernst, Neil
Quirion, Rémi
Gratton, Alain
Szyf, Moshe
Turecki, Gustavo
Publication Title: 
BMC bioinformatics

BACKGROUND: CpG islands (CGIs), clusters of CpG dinucleotides in GC-rich regions, are often located in the 5' end of genes and considered gene markers. Hackenberg et al. (2006) recently developed a new algorithm, CpGcluster, which uses a completely different mathematical approach from previous traditional algorithms. Their evaluation suggests that CpGcluster provides a much more efficient approach to detecting functional clusters or islands of CpGs. RESULTS: We systematically compared CpGcluster with the traditional algorithm by Takai and Jones (2002).

Author(s): 
Han, Leng
Zhao, Zhongming
Publication Title: 
Journal of Affective Disorders

BACKGROUND: Bipolar disorder is a complex disorder hypothesized to involve an interaction of multiple susceptibility genes and environmental factors. The environmental factors may be mediated via epigenetic mechanisms such as DNA methylation. Since a different extent of DNA methylation has recently been reported in lymphoblastoid cells derived from monozygotic twins discordant for bipolar disorder, we hypothesized that bipolar patients exhibit a different extent of leukocyte global DNA methylation compared with healthy controls.

Author(s): 
Bromberg, A.
Bersudsky, Y.
Levine, J.
Agam, G.
Publication Title: 
Biochemical and Biophysical Research Communications

Methylation occurs frequently at 5'-cytosine of the CpG dinucleotides in vertebrate genomes; however, this epigenetic feature is rarely observed in CpG islands (CGIs) or CpG clusters in the promoter regions of genes. Aberrant methylation of the promoter-associated CGIs might influence gene expression and cause carcinogenesis. Because of the functional importance, multiple algorithms have been available for identifying CGIs in a genome or a sequence.

Author(s): 
Zhao, Zhongming
Han, Leng
Publication Title: 
Journal of Neural Transmission (Vienna, Austria: 1996)

NMDA receptors and especially the NR2B receptor subtype play a crucial role during chronic ethanol consumption and alcohol withdrawal. Therefore, the NR2B receptor subtype expression in peripheral blood cells of 32 male patients suffering from alcohol dependency were assessed through quantitative RT-PCR and to explore regulating epigenetic mechanisms, a methylation analysis was conducted using bisulfite sequencing of a fragment of the NR2B promoter region.

Author(s): 
Biermann, Teresa
Reulbach, Udo
Lenz, Bernd
Frieling, Helge
Muschler, Marc
Hillemacher, Thomas
Kornhuber, Johannes
Bleich, Stefan

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