7 results on '"Dymov, Sergiy"'
Search Results
2. The signature of liver cancer in immune cells DNA methylation.
- Author
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Zhang, Yonghong, Petropoulos, Sophie, Liu, Jinhua, Cheishvili, David, Zhou, Rudy, Dymov, Sergiy, Li, Kang, Li, Ning, and Szyf, Moshe
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LIVER cancer , *IMMUNE system , *CANCER invasiveness - Abstract
Background: The idea that changes to the host immune system are critical for cancer progression was proposed a century ago and recently regained experimental support. Results: Herein, the hypothesis that hepatocellular carcinoma (HCC) leaves a molecular signature in the host peripheral immune system was tested by profiling DNA methylation in peripheral blood mononuclear cells (PBMC) and T cells from a discovery cohort (n = 69) of healthy controls, chronic hepatitis, and HCC using Illumina 450K platform and was validated in two validation sets (n= 80 and n = 48) using pyrosequencing. Conclusions: The study reveals a broad signature of hepatocellular carcinoma in PBMC and T cells DNA methylation which discriminates early HCC stage from chronic hepatitis B and C and healthy controls, intensifies with progression of HCC, and is highly enriched in immune function-related genes such as PD-1, a current cancer immunotherapy target. These data also support the feasibility of using these profiles for early detection of HCC. [ABSTRACT FROM AUTHOR]
- Published
- 2018
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3. DNA methylation of the serotonin transporter gene (SLC6A4) is associated with brain function involved in processing emotional stimuli.
- Author
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Frodl, Thomas, Szyf, Moshe, Carballedo, Angela, Ly, Victoria, Dymov, Sergiy, Vaisheva, Farida, Morris, Derek, Fahey, Ciara, Meaney, James, Gill, Michael, and Booij, Linda
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BRAIN physiology , *DNA , *ANALYSIS of covariance , *CHI-squared test , *MENTAL depression , *EMOTIONS , *GENES , *REGRESSION analysis , *RESEARCH funding , *SEROTONIN , *STATISTICS , *DATA analysis , *CASE-control method , *DATA analysis software , *DESCRIPTIVE statistics , *PHYSIOLOGY - Abstract
Background: The aim of the present study was to investigate the association of fMRI blood oxygen--level dependent (BOLD) reactivity with the level of epigenetic methylation of SLC6A4 in blood DNA from a sample of healthy participants and patients with major depressive disorder (MDD). Methods: We investigated patients with MDD and healthy controls using fMRI and an emotional attention-shifting task. We assessed site-specific DNA methylation of a previously characterized SLC6A4 region in peripheral blood DNA using pyro-sequencing. Results: Our study involved 25 patients with MDD and 35 healthy controls. Activation in the anterior insula elicited by negative emotional content was significantly positively associated with the degree of SLC6A4 methylation. Significantly negative associations were observed between activation in the posterior insula and the degree of SLC6A4 methylation when judging the geometry of pictures after seeing negative in contrast to positive emotional stimuli. Healthy controls with a high degree of SLC6A4 methylation depicted significantly more activity elicited by positive stimuli in limbic regions and more activity elicited by negative stimuli in limbic as well as cognitive control regions than those with a low degree of SLC6A4 methylation. Limitations: It is impossible to measure methylation directly in the brain and thus we assessed peripheral methylation of SLC6A4. Since the association was cross-sectional, no conclusion about cause and effect can be drawn. Conclusion: Our study provides further support to the hypothesis that particular DNA methylation states that are associated with brain function during emotion processing are detectable in the periphery. [ABSTRACT FROM AUTHOR]
- Published
- 2015
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4. DNA Methylation of the Serotonin Transporter Gene in Peripheral Cells and Stress-Related Changes in Hippocampal Volume: A Study in Depressed Patients and Healthy Controls.
- Author
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Booij, Linda, Szyf, Moshe, Carballedo, Angela, Frey, Eva-Maria, Morris, Derek, Dymov, Sergiy, Vaisheva, Farida, Ly, Victoria, Fahey, Ciara, Meaney, James, Gill, Michael, and Frodl, Thomas
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SEROTONIN transporters , *HIPPOCAMPUS physiology , *DEPRESSED persons , *ETIOLOGY of diseases , *NEURAL development , *PATHOLOGICAL psychology - Abstract
Serotonin plays an important role in the etiology of depression. Serotonin is also crucial for brain development. For instance, animal studies have demonstrated that early disruptions in the serotonin system affect brain development and emotion regulation in later life. A plausible explanation is that environmental stressors reprogram the serotonin system through epigenetic processes by altering serotonin system gene expression. This in turn may affect brain development, including the hippocampus, a region with dense serotonergic innervations and important in stress-regulation. The aim of this study was to test whether greater DNA methylation in specific CpG sites at the serotonin transporter promoter in peripheral cells is associated with childhood trauma, depression, and smaller hippocampal volume. We were particularly interested in those CpG sites whose state of methylation in peripheral cells had previously been associated with in vivo measures of brain serotonin synthesis. Thirty-three adults with Major Depressive Disorder (MDD) (23 females) and 36 matched healthy controls (21 females) were included in the study. Depressive symptoms, childhood trauma, and high-resolution structural MRI for hippocampal volume were assessed. Site-specific serotonin transporter methylation was assessed using pyrosequencing. Childhood trauma, being male, and smaller hippocampal volume were independently associated with greater peripheral serotonin transporter methylation. Greater serotonin transporter methylation in the depressed group was observed only in SSRI-treated patients. These results suggest that serotonin transporter methylation may be involved in physiological gene-environment interaction in the development of stress-related brain alterations. The results provide some indications that site-specific serotonin transporter methylation may be a biomarker for serotonin-associated stress-related psychopathology. [ABSTRACT FROM AUTHOR]
- Published
- 2015
- Full Text
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5. The methylated-DNA binding protein MBD2 enhances NGFI-A (egr-1)-mediated transcriptional activation of the glucocorticoid receptor.
- Author
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Weaver, Ian C. G., Hellstrom, Ian C., Brown, Shelley E., Andrews, Stephen D., Dymov, Sergiy, Diorio, Josie, Tie-Yuan Zhang, Moshe Szyf, and Meaney, Michael J.
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GLUCOCORTICOID receptors , *DNA-binding proteins , *HIPPOCAMPUS (Brain) , *NERVE growth factor , *MUTAGENESIS , *GENES - Abstract
Variations in maternal care in the rat influence the epigenetic state and transcriptional activity of glucocorticoid receptor (GR) gene in the hippocampus. The mechanisms underlying this maternal effect remained to be defined, including the nature of the relevant maternally regulated intracellular signalling pathways.We show here that increased maternal licking/grooming (LG), which stably enhances hippocampal GR expression, paradoxically increases hippocampal expression of the methyl-CpG binding domain protein-2 (MBD2) and MBD2 binding to the exon 17 GR promoter. Knockdown experiments of MBD2 in hippocampal primary cell culture show that MBD2 is required for activation of exon 17 GR promoter. Ectopic coexpression of nerve growth factor-inducible protein A (NGFI-A) with MBD2 in HEK 293 cells with site-directed mutagenesis of the NGFI-A response element within the methylated exon 17 GR promoter supports the hypothesis that MBD2 collaborates with NGFI-A in binding and activation of this promoter. These data suggest a possible mechanism linking signalling pathways, which are activated by behavioural stimuli and activation of target genes. [ABSTRACT FROM AUTHOR]
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- 2014
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6. The Transcription Factor Nerve Growth Factor-Inducible Protein A Mediates Epigenetic Programming: Altering Epigenetic Marks by Immediate-Early Genes.
- Author
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Weaver, Ian C. G., D'Alessio, Ana C., Brown, Shelley E., Hellstrom, Ian C., Dymov, Sergiy, Sharma, Shakti, Szyf, Moshe, and Meaney, Michael J.
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MATERNAL love , *GLUCOCORTICOID receptors , *GENE expression , *NERVE growth factor , *HIPPOCAMPUS (Brain) , *DNA , *MUTAGENESIS - Abstract
Maternal care alters epigenetic programming of glucocorticoid receptor (GR) gene expression in the hippocampus, and increased postnatal maternal licking/grooming (LG) behavior enhances nerve growth factor-inducible protein A (NGFI-A) transcription factor binding to the exon 17GR promoter within the hippocampus of the offspring. We tested the hypothesis that NGFI-A binding to the exon 17GR promoter sequence marks this sequence for histone acetylation and DNA demethylation and that such epigenetic alterations subsequently influence NGFI-A binding and GR transcription. We report that (1) NGFI-A binding to its consensus sequence is inhibited by DNA methylation, (2) NGFI-A induces the activity of exon 17GR promoter in a transient reporter assay, (3) DNA methylation inhibits exon 17GR promoter activity, and (4) whereas NGFI-A interaction with the methylated exon 17GR promoter is reduced, NGFI-A overexpression induces histone acetylation, DNA demethylation, and activation of the exon 17GR promoter in transient transfection assays. Site-directed mutagenesis assays demonstrate that NGFI-A binding to the exon 17GR promoter is required for such epigenetic reprogramming. In vivo, enhanced maternal LG is associated with increased NGFI-A binding to the exon 17GR promoter in the hippocampus of pups, and NGFI-A-bound exon 17GR promoter is unmethylated compared with unbound exon 17GRpromoter. Knockdown experiments of NGFI-A in hippocampal primary cell culture show that NGFI-A is required for serotonin-induced DNA demethylation and increased exon 17GR promoter expression. The data are consistent with the hypothesis that NGFI-A participates in epigenetic programming of GR expression. [ABSTRACT FROM AUTHOR]
- Published
- 2007
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7. Reversal of Maternal Programming of Stress Responses in Adult Offspring through Methyl Supplementation: Altering Epigenetic Marking Later in Life.
- Author
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Weaver, Ian C. G., Champagne, Frances A., Brown, Shelley E., Dymov, Sergiy, Sharma, Shakti, Meaney, Michael J., and Szyf, Moshe
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PARENTAL behavior in animals , *METHIONINE , *EXONS (Genetics) , *GLUCOCORTICOID receptors , *AMINO acids , *RATS - Abstract
Stress responses in the adult rat are programmed early in life by maternal care and associated with epigenomic marking of the hippocampal exon 17 glucocorticoid receptor (GR) promoter. To examine whether such epigenetic programming is reversible in adult life, we centrally infused the adult offspring with the essential amino acid L-methionine, a precursor to S-adenosyl-methionine that serves as the donor of methyl groups for DNA methylation. Here we report that methionine infusion reverses the effect of maternal behavior on DNA methylation, nerve growth factor-inducible protein-A binding to the exon 17 promoter, GR expression, and hypothalamic-pituitary- adrenal and behavioral responses to stress, suggesting a causal relationship among epigenomic state, GR expression, and stress responses in the adult offspring. These results demonstrate that, despite the inherent stability of the epigenomic marks established early in life through behavioral programming, they are potentially reversible in the adult brain. [ABSTRACT FROM AUTHOR]
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- 2005
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