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Assessing the influence of DNMTi on human CD8+ T cells on a global level using methylome and transcriptome analyses.

ABSTRACT: RRBS (Reduced Representation Bisulfite Sequencing) and RNA-seq were performed on human CD8+ T cells from peripheral blood of three independent healthy donors to study the influence of DNMTi on CD8+ T cells on a global level.

ORGANISM(S): Homo sapiens

PROVIDER: GSE93383 | GEO | 2021/02/08

REPOSITORIES: GEO

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Murine mammary epithelial cell methylome and ATAC-seq analyses

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2018-06-10 | GSE80181 | GEO

The Myonuclear DNA Methylome in Response to an Acute Hypertrophic Stimulus

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Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation

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2011-07-01 | E-GEOD-30253 | biostudies-arrayexpress

Analysis of DNA methylation in a three-generation family reveals widespread genetic influence on epigenetic regulation

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Targeting the ADPKD methylome using nanoparticle-mediated combination therapy

Project description:DNA methylation aberrancies are found in autosomal dominant polycystic kidney disease (ADPKD) which suggest the methylome to be a promising therapeutic target. However, the impact of combining DNA methylation inhibitors (DNMTi) and ADPKD drugs in treating ADPKD and on disease-associated methylation patterns has not been fully explored. To test this, ADPKD drugs, metformin and tolvaptan (MT), were delivered in combination with DNMTi 5-aza-2’-deoxycytidine (Aza) to 2D or 3D cystic Pkd1 heterozygous renal epithelial cells (PKD1-Het cells) as free drugs or within nanoparticles to enable direct delivery for future in vivo applications. We found Aza synergizes with MT to reduce cell viability and cystic growth. Reduced representation bisulfite sequencing (RRBS) was performed across 4 groups: PBS, Free-Aza (Aza), Free-Aza+MT (F-MTAza), and Nanoparticle-Aza+MT (NP-MTAza). Global methylation patterns showed that while Aza alone induces a unimodal intermediate methylation landscape, Aza+MT recovers the bimodality reminiscent of somatic methylomes. Importantly, site-specific methylation changes associated with F-MTAza and NP-MTAza were largely conserved including hypomethylation at ADPKD-associated genes. Notably, we report hypomethylation of cancer-associated genes implicated in ADPKD pathogenesis as well as new target genes that may provide additional therapeutic effects. Overall, this study motivates future work to further elucidate the regulatory mechanisms of observed drug synergy and apply these combination therapies in vivo.

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Genes differentially methylated after DNA methyltransferase 1 (DNMT1) knockdown in the presence or absence of early osteoblast (OB) differentiation [RRBS]

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Genome-wide DNA methylation profiling of human dorsolateral prefrontal cortex

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