ArticleMolecular cell2019
Demethylation of the Protein Phosphatase PP2A Promotes Demethylation of Histones to Enable Their Function as a Methyl Group Sink.
Article in Molecular cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Nuclear class 3 PI3K co-activates fasting-specific chromatin remodelling.Nature cell biology · 2026Article
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- Methionine Deprivation-induced Reprogramming of Hepatic Rhythms Is Mediated by Glucocorticoid Receptor.bioRxiv : the preprint server for biology · 2026Article
- Homocysteine and S-adenosyl-L-homocysteine impair development and methylation in yeast and flies.Disease models & mechanisms · 2026Article
- Metabolic stress reveals widespread accumulation of cap-unmethylated RNAs.bioRxiv : the preprint server for biology · 2026Article
- Methionine restriction alleviates kidney fibrosis through epigenetic repression of the TGF-β-Smad3-Hoxc8/P-TEFb axis.Nature communications · 2025Article
- Folic acid improves intestinal function in grass carp (Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Aurora kinase A promotes trained immunity via regulation of endogenous S-adenosylmethionine metabolism.eLife · 2025Article
- The catalytic efficiency of METTL16 affects cellular processes by governing the intracellular S-adenosylmethionine setpoint.Cell reports · 2025Article
- Mechanisms and rationales of SAM homeostasis.Trends in biochemical sciences · 2025Review
- Metabolism-driven chromatin dynamics: Molecular principles and technological advances.Molecular cell · 2025Review
- Phospholipid biosynthesis modulates nucleotide metabolism and reductive capacity.Nature chemical biology · 2025Article
- Evidence for a hydrogen sulfide-sensing E3 ligase in yeast.Genetics · 2024Article
- Sulfur starvation-induced autophagy in Saccharomyces cerevisiae involves SAM-dependent signaling and transcription activator Met4.Nature communications · 2024Article
- The SWI/SNF chromatin remodeling complex: a critical regulator of metabolism.Biochemical Society transactions · 2024Review
- Subcellular one carbon metabolism in cancer, aging and epigenetics.Frontiers in epigenetics and epigenomics · 2024Article
- Sexual differentiation in human malaria parasites is regulated by competition between phospholipid metabolism and histone methylation.Nature microbiology · 2023Article
- Methionine restriction constrains lipoylation and activates mitochondria for nitrogenic synthesis of amino acids.Nature communications · 2023Article
- Biased holoenzyme assembly of protein phosphatase 2A (PP2A): From cancer to small molecules.The Journal of biological chemistry · 2022Review
- Macrophages, Metabolites, and Nucleosomes: Chromatin at the Intersection between Aging and Inflammation.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
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.
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