Cancer growth and metastasis gene pathways are regulated by Methyl-CpG Binding Domain Protein 2 (Mbd2) in liver cancer and are altered by the ubiquitous methyl donor S-adenosyl methionine (SAM)
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ABSTRACT:
PROVIDER: PRJNA700852 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13665126_1.fastq.gz | Fastqsanger.gz | |||
| SRR13665126_2.fastq.gz | Fastqsanger.gz | |||
| SRR13665127_1.fastq.gz | Fastqsanger.gz | |||
| SRR13665127_2.fastq.gz | Fastqsanger.gz | |||
| SRR13665128_1.fastq.gz | Fastqsanger.gz |
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Project description:Perpose:We examined here whether SAM, which alters DNA methylation dynamics, interferes with the activity of Methyl-CpG Binding Domain Protein 2(Mbd2). Methods: mRNA of MBD2 knocked down of Skhep1 and HepG2 cells were generated by deep sequencing using Illumina GAIIx. DNA enriched by our designed microarray of MBD2 knocked down Skhep1 and HepG2 cells were also generated by deep sequencing using Illumina GAIIx. ChIP (Chromatin immunoprecipitation) was performed using ChIP-IT Express Kit with MBD2 antibody of SAM treated Skhep1, HepG2 and NorHep cells. concluds: SAM treatment results in reduction and redistribution of Mbd2 binding across genomic features in liver cancer cells, which is different from the response in untransformed liver cells. There is significant overlap between genes whose Mbd2 binding, DNA methylation and transcription are altered by Mbd2 depletion or SAM treatment. These data suggest that Mbd2 has a cancer specific footprint in binding, DNA methylation and transcription in liver cancer cells that is altered by SAM treatment. SAM selective impact on liver cancer cells is partially mediated by altering cancer specific Mbd2 binding. These data provide a molecular rationale for using either SAM or other Mbd2 modulators for treating/preventing liver cancer.
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Project description:Epigenetics (DNA methylation) profiling of bovine in vitro cultured expanded blastocysts (EB) comparing control non-treated expanded blastocysts with SAM-treated expanded blastocysts. S-Adenosyl methionine (SAM) is the global methyl donor providing methyl
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Project description:Transcriptome (total RNA) profiling of bovine in vitro cultured expanded blastocysts (EB) comparing control non-treated expanded blastocysts with SAM-treated expanded blastocysts. S-Adenosyl methionine (SAM) is the global methyl donor providing methyl group for variety of biomolecules such as DNA , histone, RNA, lipids and etc.
2016-02-29 | GSE75430 | GEO
Project description:Transcriptome (total RNA) profiling of bovine in vitro cultured expanded blastocysts (EB) comparing control non-treated expanded blastocysts with SAM-treated expanded blastocysts. S-Adenosyl methionine (SAM) is the global methyl donor providing methyl group for variety of biomolecules such as DNA , histone, RNA, lipids and etc. Two-condition experiment, bovine non-treated expanded blastocysts (pools of 10) vs bovine SAM-treated expanded blastocysts. Four biological replicates of each tissue were hybridized to four two-color arrays in a dye-balanced design.
2016-02-29 | E-GEOD-75430 | biostudies-arrayexpress
Project description:The Methyl-CpG-Binding Domain Protein family has been implicated in neurodevelopmental disorders. The Methyl-CpG-binding domain 2 (Mbd2) binds methylated DNA and was shown to play an important role in cancer and immunity. Some evidence linked this protein to neurodevelopment. However, its exact role in neurodevelopment and brain function is mostly unknown. Here we show that Mbd2-deficiency in mice (Mbd2-/-) results in deficits in cognitive, social and emotional functions. Mbd2 binds regulatory DNA regions of neuronal genes in the hippocampus and loss of Mbd2 alters the expression of hundreds of genes with a robust down-regulation of neuronal gene pathways. Further, a genome-wide DNA methylation analysis found an altered DNA methylation pattern in regulatory DNA regions of neuronal genes in Mbd2-/- mice. Differentially expressed genes significantly overlap with gene-expression changes observed in brain of Autism Spectrum Disorder (ASD) individuals. Notably, down-regulated genes are significantly enriched for human ortholog ASD risk-genes. Observed hippocampal morphological abnormalities were similar to those found in individuals with ASD and ASD rodent models. Mbd2 knockdown partially recapitulates the behavioral phenotypes observed in Mbd2-/- mice. These findings suggest Mbd2 is a novel epigenetic regulator of genes that are associated with ASD in humans. Mbd2 loss causes behavioral alterations that resemble those found in ASD patients.
2023-06-22 | GSE128703 | GEO
Project description:The Methyl-CpG-Binding Domain Protein family has been implicated in neurodevelopmental disorders. The Methyl-CpG-binding domain 2 (Mbd2) binds methylated DNA and was shown to play an important role in cancer and immunity. Some evidence linked this protein to neurodevelopment. However, its exact role in neurodevelopment and brain function is mostly unknown. Here we show that Mbd2-deficiency in mice (Mbd2-/-) results in deficits in cognitive, social and emotional functions. Mbd2 binds regulatory DNA regions of neuronal genes in the hippocampus and loss of Mbd2 alters the expression of hundreds of genes with a robust down-regulation of neuronal gene pathways. Further, a genome-wide DNA methylation analysis found an altered DNA methylation pattern in regulatory DNA regions of neuronal genes in Mbd2-/- mice. Differentially expressed genes significantly overlap with gene-expression changes observed in brain of Autism Spectrum Disorder (ASD) individuals. Notably, down-regulated genes are significantly enriched for human ortholog ASD risk-genes. Observed hippocampal morphological abnormalities were similar to those found in individuals with ASD and ASD rodent models. Mbd2 knockdown partially recapitulates the behavioral phenotypes observed in Mbd2-/- mice. These findings suggest Mbd2 is a novel epigenetic regulator of genes that are associated with ASD in humans. Mbd2 loss causes behavioral alterations that resemble those found in ASD patients.
2023-06-22 | GSE128612 | GEO
Project description:The Methyl-CpG-Binding Domain Protein family has been implicated in neurodevelopmental disorders. The Methyl-CpG-binding domain 2 (Mbd2) binds methylated DNA and was shown to play an important role in cancer and immunity. Some evidence linked this protein to neurodevelopment. However, its exact role in neurodevelopment and brain function is mostly unknown. Here we show that Mbd2-deficiency in mice (Mbd2-/-) results in deficits in cognitive, social and emotional functions. Mbd2 binds regulatory DNA regions of neuronal genes in the hippocampus and loss of Mbd2 alters the expression of hundreds of genes with a robust down-regulation of neuronal gene pathways. Further, a genome-wide DNA methylation analysis found an altered DNA methylation pattern in regulatory DNA regions of neuronal genes in Mbd2-/- mice. Differentially expressed genes significantly overlap with gene-expression changes observed in brain of Autism Spectrum Disorder (ASD) individuals. Notably, down-regulated genes are significantly enriched for human ortholog ASD risk-genes. Observed hippocampal morphological abnormalities were similar to those found in individuals with ASD and ASD rodent models. Mbd2 knockdown partially recapitulates the behavioral phenotypes observed in Mbd2-/- mice. These findings suggest Mbd2 is a novel epigenetic regulator of genes that are associated with ASD in humans. Mbd2 loss causes behavioral alterations that resemble those found in ASD patients.
2023-06-22 | GSE128828 | GEO
Project description:Mice deficient in MBD2 (Mbd2-/-) were treated with 2% dextran sulfate sodium or normal drinking water for 6 continuous days. A single cell suspension of colon lamina propria and epithelium was isolated, with monocytes (CD11b+ Ly6CHi, MHC-II+/-), macrophages (CD11b+ Ly6C-MHC-II+), cDC2s (CD11b- CD11c+ CD103+) and epithelial cells (CD45- EpCAM+) purified by FACS. Methyl-CpG-binding domain-2 (Mbd2) acts as an epigenetic regulator of gene expression, by linking DNA methylation to repressive chromatin structure. Although Mbd2 is widely expressed in gastrointestinal immune cells and is implicated in regulating intestinal cancer and anti-helminth responses, its role in controlling colitis has yet to be defined. Indeed, epigenetic control of gene expression in cells that regulate intestinal immunity is generally poorly understood, even though such mechanisms may explain the inability of standard genetic approaches to pinpoint the causes of conditions like inflammatory bowel disease. In this study we demonstrate a vital role for Mbd2 in regulating murine colonic inflammation. Mbd2-/- mice displayed dramatically worse pathology than wild type controls during dextran sulphate sodium (DSS) induced colitis, with increased inflammatory (IL-1β+) monocytes. Profiling of mRNA from innate immune and epithelial cell (EC) populations suggested that Mbd2 suppresses inflammation and pathology via control of innate-epithelial cell crosstalk and T cell recruitment. Consequently, restriction of Mbd2 deficiency to CD11c+ dendritic cells and macrophages, or to ECs, resulted in increased DSS colitis severity. Our identification of this dual role for Mbd2 in regulating the inflammatory capacity of both CD11c+ cells and ECs highlights how epigenetic control mechanisms may limit intestinal inflammatory responses.
2020-02-26 | GSE134281 | GEO
Project description:Mice deficient in MBD2 (Mbd2-/-) were treated with 2% dextran sulfate sodium or normal drinking water for 6 continuous days. A single cell suspension of colon lamina propria and epithelium was isolated, with monocytes (CD11b+ Ly6CHi, MHC-II+/-), macrophages (CD11b+ Ly6C-MHC-II+), cDC2s (CD11b- CD11c+ CD103+) and epithelial cells (CD45- EpCAM+) purified by FACS. Methyl-CpG-binding domain-2 (Mbd2) acts as an epigenetic regulator of gene expression, by linking DNA methylation to repressive chromatin structure. Although Mbd2 is widely expressed in gastrointestinal immune cells and is implicated in regulating intestinal cancer and anti-helminth responses, its role in controlling colitis has yet to be defined. Indeed, epigenetic control of gene expression in cells that regulate intestinal immunity is generally poorly understood, even though such mechanisms may explain the inability of standard genetic approaches to pinpoint the causes of conditions like inflammatory bowel disease. In this study we demonstrate a vital role for Mbd2 in regulating murine colonic inflammation. Mbd2-/- mice displayed dramatically worse pathology than wild type controls during dextran sulphate sodium (DSS) induced colitis, with increased inflammatory (IL-1β+) monocytes. Profiling of mRNA from innate immune and epithelial cell (EC) populations suggested that Mbd2 suppresses inflammation and pathology via control of innate-epithelial cell crosstalk and T cell recruitment. Consequently, restriction of Mbd2 deficiency to CD11c+ dendritic cells and macrophages, or to ECs, resulted in increased DSS colitis severity. Our identification of this dual role for Mbd2 in regulating the inflammatory capacity of both CD11c+ cells and ECs highlights how epigenetic control mechanisms may limit intestinal inflammatory responses.
2020-02-26 | GSE134280 | GEO
Project description:Cancer is characterised by DNA hypermethylation and gene silencing of CpG island-associated promoters, including tumour suppressor genes The methyl-CpG-binding domain (MBD) family of proteins bind to methylated DNA and can aid in the meditation of gene silencing by interaction with histone deacetylases and histone methyltransferases. However the mechanisms responsible for eliciting CpG island hypermethylation in cancer, and the potential role that MBD may proteins play in modulation of the methylome remain unclear. Our previous work demonstrated that MBD2 preferentially binds to the hypermethylated GSTP1 promoter CpG island in prostate cancer cells. Here, we use functional genetic approaches to investigate if MBD2 plays an active role in promoting DNA methylation. First, we show that loss of MBD2 results in inhibition of both maintenance and spread of de novo methylation of a transfected construct containing the GSTP1 promoter CpG island in prostate cancer cells and Mbd2-/- mouse fibroblasts. De novo methylation was rescued by transient expression of Mbd2 in Mbd2-/- cells. Second, we show that MBD2 depletion triggers significant hypomethylation genome-wide in prostate cancer cells with concomitant loss of MBD2 binding at promoter and enhancer regulatory regions. Finally, CpG islands and shores that become hypomethylated after MBD2 depletion in LNCaP cancer cells show significant hypermethylation in clinical prostate cancer, highlighting a potential active role of MBD2 in promoting cancer specific hypermethylation. Importantly, co-immunoprecipiation of MBD2 reveals that MBD2 associates with DNA methyltransferase (DNMT) enzymes 1 and 3A. Together our results demonstrate that MBD2 plays a critical role in “rewriting” the cancer methylome at specific regulatory regions.
2016-08-24 | GSE77201 | GEO