The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Douglas E Williamson - One of the best experts on this subject based on the ideXlab platform.
-
an Epigenetic Mechanism links socioeconomic status to changes in depression related brain function in high risk adolescents
Molecular Psychiatry, 2017Co-Authors: Johnna R Swartz, Ahmad R Hariri, Douglas E WilliamsonAbstract:An Epigenetic Mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents
-
an Epigenetic Mechanism links socioeconomic status to changes in depression related brain function in high risk adolescents
Molecular Psychiatry, 2017Co-Authors: Johnna R Swartz, Ahmad R Hariri, Douglas E WilliamsonAbstract:Identifying biological Mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step toward developing strategies for personalized treatment and, ultimately, prevention. Preclinical studies have identified Epigenetic modification of gene expression as one such Mechanism. Recent clinical studies have suggested that Epigenetic modification, particularly methylation of gene regulatory regions, also acts to shape human brain function associated with risk for mental illness. However, it is not yet clear whether differential gene methylation as a function of adversity contributes to the emergence of individual risk for mental illness. Using prospective longitudinal Epigenetic, neuroimaging and behavioral data from 132 adolescents, we demonstrate that changes in gene methylation associated with lower socioeconomic status (SES) predict changes in risk-related brain function. Specifically, we find that lower SES during adolescence is associated with an increase in methylation of the proximal promoter of the serotonin transporter gene, which predicts greater increases in threat-related amygdala reactivity. We subsequently demonstrate that greater increases in amygdala reactivity moderate the association between a positive family history for depression and the later manifestation of depressive symptoms. These initial results suggest a specific biological Mechanism through which adversity contributes to altered brain function, which in turn moderates the emergence of general liability as individual risk for mental illness. If replicated, this prospective pathway may represent a novel target biomarker for intervention and prevention among high-risk individuals.
Xiaofeng Wang - One of the best experts on this subject based on the ideXlab platform.
-
abstract lb 096 smarcb1 mediated swi snf complex function is essential for enhancer regulation
Cancer Research, 2017Co-Authors: Xiaofeng Wang, Ryan S Lee, Burak H Alver, Jeffrey R Haswell, Su Wang, Emma C Troisi, Bradley E Bernstein, Peter J Park, Charles W M RobertsAbstract:The gene encoding SMARCB1 (SNF5/INI1/BAF47), a core subunit of the SWI/SNF (BAF) chromatin remodeling complex, is biallelically inactivated in nearly all rhabdoid tumors (RTs), highly aggressive and lethal cancers of early childhood. RTs are among the most genomically stable cancers, suggesting an Epigenetic Mechanism by which SMARCB1 loss drives cancer. Here, we show that despite having indistinguishable mutational landscapes, human RTs show distinct H3K27ac signatures at enhancers that reveal remnants of differentiation programs. In elucidating the Mechanism underlying RTs, we find that SMARCB1 is not only essential for the integrity and abundance of SWI/SNF complexes, but also facilitates their targeting to appropriate enhancers. Loss of SMARCB1 alters enhancer targeting—markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers (SEs). We show that these retained SEs are essential for RT survival, including some that are shared across all RT types, such as SPRY1, and other lineage-specific SEs like SOX2 in brain-derived RTs. Taken together, our findings reveal a novel chromatin-based Epigenetic Mechanism underlying the tumor suppressive activity of SMARCB1. Citation Format: Xiaofeng Wang, Ryan Lee, Burak Alver, Jeffrey Haswell, Su Wang, Emma Troisi, Bradley Bernstein, Peter Park, Charles Roberts. SMARCB1-mediated SWI/SNF complex function is essential for enhancer regulation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr LB-096. doi:10.1158/1538-7445.AM2017-LB-096
-
smarcb1 mediated swi snf complex function is essential for enhancer regulation
Nature Genetics, 2017Co-Authors: Xiaofeng Wang, Ryan S Lee, Burak H Alver, Jeffrey R Haswell, Su Wang, Jakub Mieczkowski, Yotam DrierAbstract:SMARCB1 (also known as SNF5, INI1, and BAF47), a core subunit of the SWI/SNF (BAF) chromatin-remodeling complex, is inactivated in nearly all pediatric rhabdoid tumors. These aggressive cancers are among the most genomically stable, suggesting an Epigenetic Mechanism by which SMARCB1 loss drives transformation. Here we show that, despite having indistinguishable mutational landscapes, human rhabdoid tumors exhibit distinct enhancer H3K27ac signatures, which identify remnants of differentiation programs. We show that SMARCB1 is required for the integrity of SWI/SNF complexes and that its loss alters enhancer targeting-markedly impairing SWI/SNF binding to typical enhancers, particularly those required for differentiation, while maintaining SWI/SNF binding at super-enhancers. We show that these retained super-enhancers are essential for rhabdoid tumor survival, including some that are shared by all subtypes, such as SPRY1, and other lineage-specific super-enhancers, such as SOX2 in brain-derived rhabdoid tumors. Taken together, our findings identify a new chromatin-based Epigenetic Mechanism underlying the tumor-suppressive activity of SMARCB1.
Johnna R Swartz - One of the best experts on this subject based on the ideXlab platform.
-
an Epigenetic Mechanism links socioeconomic status to changes in depression related brain function in high risk adolescents
Molecular Psychiatry, 2017Co-Authors: Johnna R Swartz, Ahmad R Hariri, Douglas E WilliamsonAbstract:An Epigenetic Mechanism links socioeconomic status to changes in depression-related brain function in high-risk adolescents
-
an Epigenetic Mechanism links socioeconomic status to changes in depression related brain function in high risk adolescents
Molecular Psychiatry, 2017Co-Authors: Johnna R Swartz, Ahmad R Hariri, Douglas E WilliamsonAbstract:Identifying biological Mechanisms through which the experience of adversity emerges as individual risk for mental illness is an important step toward developing strategies for personalized treatment and, ultimately, prevention. Preclinical studies have identified Epigenetic modification of gene expression as one such Mechanism. Recent clinical studies have suggested that Epigenetic modification, particularly methylation of gene regulatory regions, also acts to shape human brain function associated with risk for mental illness. However, it is not yet clear whether differential gene methylation as a function of adversity contributes to the emergence of individual risk for mental illness. Using prospective longitudinal Epigenetic, neuroimaging and behavioral data from 132 adolescents, we demonstrate that changes in gene methylation associated with lower socioeconomic status (SES) predict changes in risk-related brain function. Specifically, we find that lower SES during adolescence is associated with an increase in methylation of the proximal promoter of the serotonin transporter gene, which predicts greater increases in threat-related amygdala reactivity. We subsequently demonstrate that greater increases in amygdala reactivity moderate the association between a positive family history for depression and the later manifestation of depressive symptoms. These initial results suggest a specific biological Mechanism through which adversity contributes to altered brain function, which in turn moderates the emergence of general liability as individual risk for mental illness. If replicated, this prospective pathway may represent a novel target biomarker for intervention and prevention among high-risk individuals.
Hisato Kobayashi - One of the best experts on this subject based on the ideXlab platform.
-
paternal age affects offspring via an Epigenetic Mechanism involving rest nrsf
EMBO Reports, 2021Co-Authors: Kaichi Yoshizaki, Ryuichi Kimura, Takako Kikkawa, Hisato Kobayashi, Shinya Oki, Lingling Mai, Kohei KoikeAbstract:Advanced paternal age can have deleterious effects on various traits in the next generation. Here, we establish a paternal-aging model in mice to understand the molecular Mechanisms of transgenerational Epigenetics. Whole-genome target DNA methylome analyses of sperm from aged mice reveal more hypo-methylated genomic regions enriched in REST/NRSF binding motifs. Gene set enrichment analyses also reveal the upregulation of REST/NRSF target genes in the forebrain of embryos from aged fathers. Offspring derived from young mice administrated with a DNA de-methylation drug phenocopy the abnormal vocal communication of pups derived from aged fathers. In conclusion, hypo-methylation of sperm DNA can be a key molecular feature modulating neurodevelopmental programs in offspring by causing fluctuations in the expression of REST/NRSF target genes.
-
paternal age affects offspring s behavior possibly via an Epigenetic Mechanism recruiting a transcriptional repressor rest
bioRxiv, 2019Co-Authors: Kaichi Yoshizaki, Ryuichi Kimura, Kentaro Mochizuki, Takako Kikkawa, Hitoshi Inada, Hisato Kobayashi, Shinya Oki, Kohei Koike, Tasuku KoikeAbstract:Abstract Advanced paternal age has deleterious effects on mental health of next generation. Using a mouse model, we have confirmed that offspring derived from aged fathers showed impairments in behavior and abnormalities in the brain structure and activity. Comprehensive target DNA methylome analyses revealed in aged sperm more hypo-methylated genomic regions, in which REST/NRSF binding motif was enriched. Gene set enrichment analyses also identified enrichment of “REST/NRSF target genes”, in addition to “Late-fetal genes” and autism spectrum disorder-related “SFARI genes”, in up-regulated genes of developing brains from aged father. Indeed, gene sets near hypo-methylated genomic regions with REST/NRSF binding motif were also enriched in up-regulated genes of developing brains. Taken altogether, DNA hypo-methylation due to paternal aging in sperm will induce leaky expression of REST/NRSF target genes in the developing brain, thereby causing neuronal abnormalities and subsequent behavioral alteration in offspring.
Yung-jue Bang - One of the best experts on this subject based on the ideXlab platform.
-
akap12 gravin is inactivated by Epigenetic Mechanism in human gastric carcinoma and shows growth suppressor activity
Oncogene, 2004Co-Authors: Moon Chang Choi, Hyun Soon Jong, Sanghyun Song, Yung-jue BangAbstract:AKAP12/Gravin is inactivated by Epigenetic Mechanism in human gastric carcinoma and shows growth suppressor activity
-
transcriptional silencing of the dlc 1 tumor suppressor gene by Epigenetic Mechanism in gastric cancer cells
Oncogene, 2003Co-Authors: Tai Young Kim, Hyun Soon Jong, Sanghyun Song, Alexandre Dimtchev, Sookjung Jeong, Jung Weon Lee, Taeyou Kim, Noe Kyeong Kim, Mira Jung, Yung-jue BangAbstract:DLC-1 (deleted in liver cancer) gene is frequently deleted in hepatocellular carcinoma. However, little is known about the genetic status and the expression of this gene in gastric cancer. In this study, Northern and Southern analysis showed that seven of nine human gastric cancer cell lines did not express DLC-1 mRNA, but contained the DLC-1 gene. To identify the Mechanism of the loss of DLC-1 mRNA expression in these cell lines, we investigated the methylation status of DLC-1 gene by using methylation-specific PCR (MSP) and Southern blot, and found that five of seven DLC-1 nonexpressing gastric cancer cell lines were methylated in the DLC-1 CpG island. Treatment with 5-aza-2'-deoxycytidine (5-Aza-dC) induced DLC-1 mRNA expression in the gastric cancer cell lines that have the methylated alleles. Studies using SNU-601 cell line with methylated DLC-1 alleles revealed that nearly all CpG sites within DLC-1 CpG island were methylated, and that the in vitro methylation of the DLC-1 promoter region is enough to repress DLC-1 mRNA expression, regardless of the presence of transcription factors capable of inducing this gene. In all, 29 of 97 (30%) primary gastric cancers were also shown to be methylated, demonstrating that methylation of the DLC-1 CpG island is not uncommon in gastric cancer. In addition, we demonstrated that DLC-1 mRNA expression was induced, and an increase in the level of acetylated H3 and H4 was detected by the treatment with trichostatin A (TSA) in two DLC-1 nonexpressing cell lines that have the unmethylated alleles. Taken together, the results of our study suggest that the transcriptional silencing of DLC-1, by Epigenetic Mechanism, may be involved in gastric carcinogenesis.