Demethylation of the protein phosphatase PP2A promotes the demethylation of histones to enable their function as a methyl group sink
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA497903 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Dysregulation of chromatin methylation is strongly linked to defects in cellular differentiation as well as a variety of cancers. How cells regulate the opposing activities of histone methyltransferase and demethylase enzymes to set the methylation status of the epigenome for proper control of gene expression and metabolism remains poorly understood. Here, we show that loss of methylation of the major phosphatase PP2A in response to methionine starvation activates the demethylation of histones through hyperphosphorylation of specific demethylase enzymes. In parallel, this regulatory mechanism enables cells to preserve SAM by increasing SAH to limit SAM consumption by methyltransferase enzymes. Mutants lacking the H3K36 demethylase Rph1 exhibit elevated SAM levels and are dependent on cysteine due to reduced capacity to sink the methyl groups of SAM. Therefore, PP2A directs the methylation status of histones by regulating the phosphorylation status of histone demethylase enzymes in response to SAM levels.
2019-02-15 | GSE121635 | GEO
Project description:Dysregulation of chromatin methylation is associated with defects in cellular differentiation as well as a variety of cancers. How cells regulate the opposing activities of histone methyltransferase and demethylase enzymes to set the methylation status of the epigenome for proper control of gene expression and metabolism remains poorly understood. Here, we show that loss of methylation of the major phosphatase PP2A in response to methionine starvation activates the demethylation of histones through hyperphosphorylation of specific demethylase enzymes. In parallel, this regulatory mechanism enables cells to preserve SAM by increasing SAH to limit SAM consumption by methyltransferase enzymes. Mutants lacking the PP2A methyltransferase or the effector H3K36 demethylase Rph1 exhibit elevated SAM levels and are dependent on cysteine due to reduced capacity to sink the methyl groups of SAM. Therefore, PP2A directs the methylation status of histones by regulating the phosphorylation status of histone demethylase enzymes in response to SAM levels.
| S-EPMC6628921 | biostudies-literature
Project description:Protein phosphatase 2A (PP2A), a serine/threonine phosphatase, has been shown to control T cell function. We found that in vitro activated B cells and B cells from various lupus-prone mice and patients with systemic lupus erythematosus display increased PP2A activity. To understand the contribution of PP2A to B cell function, we generated a Cd19CrePpp2r1aflox/flox (flox/flox) mouse which lacks functional PP2A only in B cells. Flox/flox mice displayed reduced spontaneous germinal center formation and decreased responses to T-dependent and T-independent antigens while their B cells responded poorly in vitro to stimulation with an anti-CD40 antibody or CpG in the presence of IL-4. Transcriptome and metabolome studies revealed altered NAD and purine/pyrimidine metabolism and increased expression of purine nucleoside phosphorylase in PP2A-deficient B cells. Our results demonstrate that PP2A is required for optimal B cell function and may contribute to increased B cell activity in systemic autoimmunity.
2020-02-04 | GSE144700 | GEO
Project description:The yeast PP2A-Cdc55 Serine/Threonine phosphatase regulates transcription under certain conditions. It is required for full activation of the environmental stress response mediated by the transcription factors Msn2 and Msn4. PP2A-Cdc55 contributes to sustained nuclear accumulation of Msn2 and Msn4 and extended chromatin recruitment under stress conditions such as hyperosmolarity stress. Transcript profiles of Msn2 and Msn4 double mutants are similar to cdc55 and the corresponding triple mutants. This argues for a Msn2/4 specific function of PP2A-Cdc55. Time course of 10 20 and 30 minutes hyperosmolarity treated yeast cells of wild type (W303), msn2msn4, cdc55, msn2msn5cdc55 genetic background.
2012-06-07 | E-GEOD-38565 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE38565: The yeast PP2A-CDC55 phosphatase regulates the transcriptional response to hyperosmolarity stress by regulating Msn2 and Msn4 [Time course 1] GSE42033: The yeast PP2A-CDC55 phosphatase regulates the transcriptional response to hyperosmolarity stress by regulating Msn2 and Msn4 [Time course 2] Refer to individual Series
2012-11-06 | E-GEOD-42034 | biostudies-arrayexpress
Project description:The yeast PP2A-Cdc55 Serine/Threonine phosphatase regulates transcription under certain conditions. It is required for full activation of the environmental stress response mediated by the transcription factors Msn2 and Msn4. PP2A-Cdc55 contributes to sustained nuclear accumulation of Msn2 and Msn4 and extended chromatin recruitment under stress conditions such as hyperosmolarity stress. Transcript profiles of Msn2 and Msn4 double mutants are similar to cdc55 and the corresponding triple mutants. This argues for a Msn2/4 specific function of PP2A-Cdc55. Time course of 0, 10 20 and 30 minutes hyperosmolarity treated yeast cells of msn2msn4 or msn2msn4cdc55 genetic background, both carrying plasmid pMsn2pMsn2DNES; reference hybridization: untreated W303 msn2msn4 pMsn2pMsn2DNES labelled with Cy3
2012-11-06 | E-GEOD-42033 | biostudies-arrayexpress
Project description:Source-to-sink carbon (C) allocation driven by the sink strength, i.e., the ability of a sink organ to import C, plays a central role in tissue growth and biomass productivity. However, molecular drivers of sink strength have not been thoroughly characterized in trees. Auxin, as a major plant phytohormone, regulates the mobilization of photoassimilates in source tissues and elevates the translocation of carbohydrates toward sink organs, including roots. In this study, we used an ‘auxin-stimulated carbon sink’ approach to understand the molecular processes involved in the long-distance source-sink C allocation in poplar. Poplar cuttings were foliar sprayed with polar auxin transport modulators, including auxin enhancers (AE) (i.e., IBA and IAA) and auxin inhibitor (AI) (i.e., NPA), followed by a comprehensive analysis of leaf, stem, and root tissues using biomass evaluation, phenotyping, C isotope labeling, metabolomics, and transcriptomics approaches. Auxin modulators altered root dry weight and branching pattern, and AE increased photosynthetically fixed C allocation from leaf to root tissues. The transcriptome analysis identified highly expressed genes in root tissue under AE condition including transcripts encoding polygalacturonase and β-amylase that could increase the sink size and activity. Metabolic analyses showed a shift in overall metabolism including an altered relative abundance levels of galactinol, and an opposite trend in citrate levels in root tissue under AE and AI conditions. In conclusion, we postulate a model suggesting that the source-sink C relationships in poplar could be fueled by mobile sugar alcohols, starch metabolism-derived sugars, and TCA-cycle intermediates as key molecular drivers of sink strength.
2023-05-15 | GSE232245 | GEO
Project description:Soybean plants that do not produce a sink, such as depodded or male sterile plants, exhibit physiological and morphological changes during the reproductive stages, including increased levels of nitrogen and starch in the leaves and a delayed senescence. To identify transcriptional changes that occur in leaves of sink-limited plants, we used RNAseq to compare gene expression levels in trifoliate leaves from depodded and ms6 male sterile plants and control plants. In sink-limited tissues, we observed a deferral of the expression of senescence-associated genes and a continued high expression of genes associated with the maturity phase of leaf development. We identified GO-terms associated with growth and development and storage protein in sink limited tissues. We also identified that the bHLH. ARFs, and SBP transcription factors were expressed in sink limited tissues while the senescing control leaves expressed WRKY and NAC transcription factors. We identified genes that were not expressed during normal leaf development but highly expressed in sink-limited plants, including the D4 “non-yellowing” gene. These changes highlighted several metabolic pathways that were involved in distinct modes of resource parttioning in the “stay green” leaves.
2017-07-20 | GSE85714 | GEO
Project description:Efficient release of promoter-proximally paused Pol II into productive elongation is essential for gene expression. Recently, we reported that the Integrator complex can bind paused Pol II and drive premature transcription termination, potently attenuating the activity of target genes. Premature termination requires RNA cleavage by the endonuclease subunit of Integrator, but the roles of other Integrator subunits in gene regulation have yet to be elucidated. Here, we report that Integrator subunit 8 (IntS8) is critical for transcription repression through its association with Protein Phosphatase 2A (PP2A). We find that Integrator-bound PP2A dephosphorylates the Pol II C-terminal domain and Spt5, and prevents the transition to productive elongation. Blocking PP2A association with Integrator thus stimulates pause release and gene activation. These results reveal a second catalytic function associated with Integrator-mediated transcription termination, and suggest a new model for the control of productive elongation involving active competition between transcriptional kinases and phosphatases.
2020-10-06 | GSE150844 | GEO
Project description:The yeast PP2A-Cdc55 Serine/Threonine phosphatase regulates transcription under certain conditions. It is required for full activation of the environmental stress response mediated by the transcription factors Msn2 and Msn4. PP2A-Cdc55 contributes to sustained nuclear accumulation of Msn2 and Msn4 and extended chromatin recruitment under stress conditions such as hyperosmolarity stress. Transcript profiles of Msn2 and Msn4 double mutants are similar to cdc55 and the corresponding triple mutants. This argues for a Msn2/4 specific function of PP2A-Cdc55.
2012-06-08 | GSE38565 | GEO