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A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes

ABSTRACT: A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes

PROVIDER: PRJNA512180 | ENA |

REPOSITORIES: ENA

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A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes [Bisulfite-seq]

Project description:A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes [Bisulfite-seq]

| PRJNA511872 | ENA

A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes [RNA-seq]

Project description:A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes [RNA-seq]

| PRJNA512181 | ENA

A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes [ChIP-seq]

Project description:A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes [ChIP-seq]

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A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes [RNA-seq]

Project description:We found SUVH-SDJ complex occupies promoter methylated genes and promotes the expression of these genes.

2018-12-30 | GSE124485 | GEO

A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes [ChIP-seq]

Project description:We found SUVH-SDJ complex occupies promoter methylated genes and promotes the expression of these genes.

2018-12-27 | GSE124377 | GEO

A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes [Bisulfite-seq]

Project description:We found SUVH-SDJ complex occupies promoter methylated genes and promotes the expression of these genes.

2018-12-27 | GSE124376 | GEO

A methylated-DNA-binding complex required for plant development mediates transcriptional activation of promoter methylated genes

Project description:This SuperSeries is composed of the SubSeries listed below.

2018-12-30 | GSE124486 | GEO

MBD2a-NuRD Binds to the Methylated γ-Globin Gene Promoter and Uniquely Forms a Complex Required for Silencing of HbF Expression

Project description:During human development, there is a switch in the erythroid compartment at birth that results in silencing of expression of fetal hemoglobin (HbF). Reversal of this silencing has been shown to be effective in overcoming the pathophysiologic defect in sickle cell anemia. Among the many transcription factors and epigenetic effectors that are known to mediate HbF silencing, two of the most potent are BCL11A and MBD2-NuRD. In this report we present direct evidence that MBD2- NuRD occupies the γ-globin gene promoter in adult erythroid cells and positions a nucleosome there that results in a closed chromatin conformation that prevents binding of the transcriptional activator, NF-Y. We show that the specific isoform, MBD2a, is required for the formation and stable occupancy of this repressor complex that includes BCL11A, MBD2a-NuRD and the arginine methyltransferase, PRMT5. The methyl cytosine binding preference and the arginine rich (GR) domain of MBD2a are required for high affinity binding to methylated γ-globin gene proximal promoter DNA sequences. Mutation of the methyl cytosine binding domain of MBD2 results in a variable but consistent loss of γ-globin gene silencing, in support of the importance of promoter methylation. The GR domain of MBD2a is also required for recruitment of PRMT5, which in turn results in placement of the repressive chromatin mark H3K8me2s at the promoter. These findings 2 support a unified model that integrates the respective roles of BCL11A, MBD2a-NuRD, PRMT5 and DNA methylation in HbF silencing.

2023-06-28 | GSE224834 | GEO

MBD2a-NuRD Binds to the Methylated γ-Globin Gene Promoter and Uniquely Forms a Complex Required for Silencing of HbF Expression

Project description:MBD2a-NuRD Binds to the Methylated γ-Globin Gene Promoter and Uniquely Forms a Complex Required for Silencing of HbF Expression

| PRJNA932758 | ENA

VRK1 is required in VRK2-methylated cancers of the nervous system

Project description:Collateral lethality occurs when loss of one paralog renders cancer cells dependent on the remaining paralog. Combining genome scale CRISPR/Cas9 screens coupled with RNA-sequencing in over 900 cancer cell lines, we found that cancers of nervous system lineage, including adult and pediatric gliomas and neuroblastomas, required the nuclear kinase Vaccinia-Related Kinase 1 (VRK1) for their survival. VRK1 dependency was inversely correlated with expression of its paralog VRK2. VRK2 knockout in VRK2-expressing cell lines sensitized cells to VRK1 knockout, and conversely, VRK2 overexpression increased cell fitness in VRK1-dependent cell lines upon suppression of VRK1. DNA methylation of the VRK2 promoter was associated with low VRK2 expression in human neuroblastomas, and adult and pediatric gliomas. Mechanistically, depletion of VRK1 reduced Barrier-to-Autointegration Factor (BAF) phosphorylation, induced abnormal chromosome segregation. and dysregulated nuclear membrane re-formation following mitosis, resulting in increased DNA damage and apoptosis. Together, these observations identify VRK1 as a synthetic lethal target in VRK2-methylated adult and pediatric gliomas and neuroblastomas.

2022-09-06 | PXD030599 | Pride

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