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Engineering epigenetic memory requires co-targeting of histone methylatransferases and DNA methylatransferases [Methylation]

ABSTRACT: Engineering epigenetic memory requires co-targeting of histone methylatransferases and DNA methylatransferases [Methylation]

PROVIDER: PRJNA510108 | ENA |

REPOSITORIES: ENA

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Engineering epigenetic memory requires co-targeting of histone methylatransferases and DNA methylatransferases

Project description:Engineering epigenetic memory requires co-targeting of histone methylatransferases and DNA methylatransferases

| PRJNA510116 | ENA

Engineering epigenetic memory requires co-targeting of histone methylatransferases and DNA methylatransferases [ChIP-seq]

Project description:Engineering epigenetic memory requires co-targeting of histone methylatransferases and DNA methylatransferases [ChIP-seq]

| PRJNA510113 | ENA

Engineering epigenetic memory requires co-targeting of histone methylatransferases and DNA methylatransferases [Methylation]

Project description:Rewriting of the epigenome has risen as a promising alternative to gene editing for precision medicine. In nature, epigenetic silencing can result in complete attenuation of target gene expression over multiple mitotic divisions. However, persistent repression has been difficult to achieve using targeted systems. Here, we report that robust and persistent epigenetic memory required both a DNA methyltransferase (DNMT3A-dCas9) and a histone methyltransferase (Ezh2-dCas9 or KRAB-dCas9). DNMT3A-dCas9 was dependent on full-length DNMT3L for maximal activity. Co-targeting with Ezh2-dCas9, DNMT3A-dCas9 and DNMT3L induced long-term HER2 repression over at least 50 days and maintained a heterochromatic environment. Interestingly, substitution of Ezh2-dCas9 for KRAB-dCas9 enabled long-term repression at some target genes (e.g., SNURF) but not at HER2, at which H3K9me3 and DNA methylation were transiently acquired and subsequently lost. Off-target DNA hypermethylation occurred at many individual CpG sites but rarely at multiple CpGs in a single promoter, consistent with no detectable effect on transcription at the loci tested. Conversely, robust hypermethylation was observed at HER2. These data demonstrate that targeting different combinations of histone and DNA methyltransferases is required to achieve maximal repression at different loci in the same cell, or the same locus in different cells.

2019-05-07 | GSE123830 | GEO

Engineering epigenetic memory requires co-targeting of histone methylatransferases and DNA methylatransferases [ChIP-seq]

2019-05-07 | GSE123882 | GEO

Engineering epigenetic memory requires co-targeting of histone methylatransferases and DNA methylatransferases

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

2019-05-07 | GSE123885 | GEO

Induction of autonomous memory alveolar macrophages requires T-cell help and is critical to trained immunity

Project description:Innate immune memory is a new important area of research. However, innate immune memory at the major mucosal sites remains poorly understood. Here we show that respiratory viral infection induces long-lasting memory alveolar macrophages (AM). Memory AM are programed to express high MHC II, carry a defense-ready gene signature, and produce, upon re-stimulation, neutrophil chemokines. Using a multitude of approaches, we reveal that the priming, but not maintenance, of memory AM requires the help from effector CD8 T cells. T cells jump-start this process in AM via IFN-γ production. We further find that formation/maintenance of memory AM are independent of monocytes or bone marrow progenitors. Finally, we demonstrate that memory AM are poised for robust trained immunity against bacterial infection in the lung via rapid induction of chemokines and neutrophilia. Our study thus establishes a new paradigm of immunological memory formation whereby adaptive T-lymphocytes render innate memory of mucosal-associated macrophages.

2018-11-06 | GSE118512 | GEO

Long-lasting memory of jasmonic acid-dependent immunity requires DNA demethylation and ARGONAUTE1

Project description:Long-lasting memory of jasmonic acid-dependent immunity requires DNA demethylation and ARGONAUTE1

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Fluid-electrolyte homeostasis requires histone deacetylase function

Project description:Fluid-electrolyte homeostasis requires histone deacetylase function

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High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

Project description:High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

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High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function

Project description:High recallability of memory B cells requires ZFP318-dependent transcriptional regulation of mitochondrial function