M6A directs the demethylation of histone H3K9me2 co-transcriptionall
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ABSTRACT:
PROVIDER: PRJNA643545 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12129100_1.fastq.gz | Fastqsanger.gz | |||
| SRR12129100_2.fastq.gz | Fastqsanger.gz | |||
| SRR12129101_1.fastq.gz | Fastqsanger.gz | |||
| SRR12129101_2.fastq.gz | Fastqsanger.gz | |||
| SRR12129102_1.fastq.gz | Fastqsanger.gz |
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Project description:Here we show the repressive H3K9me2 mark is specifically removed by the induction of m6A-modified transcripts. We demonstrate that the methyltransferase METTL3/METTL14 regulates H3K9me2 modification. We observed a genome-wide correlation between m6A and occupancy by the H3K9me2 demethylase KDM3B, and we found m6A reader YTHDC1 physically interacts and recruits KDM3B to m6A-associated chromatin regions, promoting H3K9me2 demethylation and gene expression. This study establishes a direct link between m6A and dynamic chromatin modification and provides mechanistic insight into the co-transcriptional interplay between RNA modification and histone modifications.
2020-07-01 | GSE153651 | GEO
Project description:Histone methylation patterns regulate gene expression and are highly dynamic during development. The erasure of histone methylation is carried out by histone demethylase enzymes. We had previously shown that vitamin C enhances the activity of Tet enzymes in embryonic stem (ES) cells, leading to DNA demethylation and activation of germline genes. We report here that vitamin C induces a remarkably specific demethylation of histone H3 lysine 9 dimethylation (H3K9me2) in ES cells. Vitamin C treatment reduces global levels of H3K9me2, but not other histone methylation marks analyzed, as measured by Western blot, immunofluorescence and mass spectrometry. Vitamin C leads to widespread loss of H3K9me2 at large chromosomal domains as well as gene promoters and repeat elements. Vitamin C-induced loss of H3K9me2 occurs rapidly within 24 hours and is reversible. Importantly, we found that the histone demethylases Kdm3a and Kdm3b are required for vitamin C-induced demethylation of H3K9me2. Moreover, we show that vitamin C-induced Kdm3a/b-mediated H3K9me2 demethylation and Tet-mediated DNA demethylation are independent processes. Lastly, we document Kdm3a/b are partially required for the up-regulation of germline genes by vitamin C. These results reveal a specific role for vitamin C in histone demethylation in ES cells, and document that DNA methylation and H3K9me2 cooperate to silence germline genes in pluripotent cells.
2017-06-30 | GSE84009 | GEO
Project description:N6-methyladenosine (m6A) is the most abundant internal modification on mammalian messenger RNA (mRNA). It is installed by a writer complex and can be reversed by erasers such as the fat mass and obesity-associated protein (FTO). Despite extensive research, the primary physiological substrates of FTO in mammalian tissues and development remain elusive. Here, we show that FTO mediates m6A demethylation of long-interspersed element-1 (LINE1) RNA in mouse embryonic stem cells (mESCs), regulating LINE1 RNA abundance and the local chromatin state, which in turn modulates transcription of LINE1-containing genes. FTO-mediated LINE1 RNA m6A demethylation also plays regulatory roles in shaping chromatin state and gene expression during mouse oocyte and embryonic development. Our results suggest broad effects of LINE1 RNA m6A demethylation by FTO in mammals.
2022-05-05 | GSE151780 | GEO
Project description:N6-methyladenosine (m6A) is the most abundant internal modification in mammalian messenger RNA (mRNA). It is installed by writer proteins and can be reversed by erasers. FTO was the first RNA demethylase shown to catalyze oxidative demethylation of m6A in RNA. Despite extensive studies, the main physiological substrates of FTO and the related functional pathways remain elusive in many systems, in particular during early mammalian development. Here, we show that FTO mediates the m6A demethylation of chromosome-associated repeat RNAs in mouse embryonic stem cells (mESCs), especially the long-interspersed element-1 family (LINE1) RNA, thereby affecting their abundances to regulate chromatin state.
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Project description:All living cells require a minimal iron threshold to sustain anabolic metabolism. However, the mechanisms by which cells sense iron to regulate anabolic processes are unclear. Here, we report a universal eukaryotic pathway for iron sensing in which molecular iron is required to sustain active histone demethylation and maintain the expression of critical components of the pro-anabolic mTORC1 pathway. Specifically, we identify the iron-binding histone-demethylase KDM3B as an intrinsic iron sensor that regulates mTORC1 activity by demethylating H3K9me2 at enhancers of a high-affinity leucine transporter and RAPTOR. By directly suppressing leucine availability and RAPTOR levels, iron deficiency (ID) supersedes other nutrient inputs into mTORC1. This process occurs in vivo, and is not an indirect effect by canonical iron-utilizing pathways. These data demonstrate a novel mechanism of eukaryotic iron sensing through dynamic chromatin remodeling and repression of mTORC1 mediated anabolism. Due to ancestral eukaryotes sharing homologues of KDMs and mTORC1 core components, this pathway likely predated the emergence of the other kingdom-specific nutrient sensors for mTORC1.
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Project description:FTO, the first RNA demethylase discovered, mediates the demethylation of N6-methyladenosine (m6A), installed internally on messenger RNA, and N6,2′-O-dimethyladenosine (m6Am), occurring at the +1 position from the 5’ cap. Despite extensive recent research on FTO, its physiological impact on cellular processes has yet to be fully elucidated. Here, we demonstrate that the cellular distribution of FTO is distinct among different cell lines, which critically affects the access of FTO to different RNA substrates. FTO binds multiple RNA substrates, including mRNA, U6 RNA, and tRNA. It mainly targets internal m6A when located in the cell nucleus and preferentially demethylates m6Am when residing in the cytoplasm. The expression levels of transcripts containing internal m6A are associated with the alteration of the FTO more so than transcripts containing m6Am. We also discover that N1-methyladenosine (m1A) in tRNA is a main substrate of FTO, with the FTO-catalyzed demethylation of target tRNAs repressing protein synthesis. Collectively, FTO-mediated RNA demethylation affects both mRNA level and translation through distinct pathways.
2018-09-14 | GSE106395 | GEO
Project description:Head and neck squamous cell carcinoma (HNSC) is one of the most common malignant cancers worldwide. However, it is always detected at an advanced stage because of a lack of biomarkers for early diagnosis. Here, we identify the RNA binding motif protein 33 (RBM33) is commonly up-regulated in HNSC and it is essential for tumorigenesis. Mechanistically, RBM33 is an m6A reader protein and forms a complex with ALKBH5. RBM33 plays crucial roles in ALKBH5-mediated mRNA m6A demethylation not only by recruitment ALKBH5 to substrate but also activation its demethylase activity through inhibition it’s SUMOylation. Moreover, global transcriptomic and epitranscriptomic analyses identify that DDIT4 is a functional downstream target gene for RBM33 in HNSC and RBM33-mediated HNSC tumorigenesis by inhibition the mTOR pathway through the inhibition of m6A-dependent DDIT4 mRNA decay. Taken together, our study uncovers a novel molecular mechanism that RBM33/ALKBH5/m6A/DDIT4/mTOR axis regulates HNSC progression through the inhibition of mTOR pathway and targeting RBM33 may be a promising strategy for HNSC treatment.
2023-09-05 | GSE242276 | GEO
Project description:We analyzed the genome-wide chromatin states in Zscan4 positive ES cells (Em+) and Zscan4 negative ES cells (Em-) by using FACS-sorted MC1-ZE7 ES cells. H3K27 hyperacetylation and DNA demethylation were detected in heterochromatic regions of Em+ cells. These results suggested that the heterochromatin is activated in Zscan4 positive state. H3K9me2 in Zscan4 positive and negative cells
2015-09-10 | E-GEOD-58617 | biostudies-arrayexpress
Project description:Histone H3 lysine 9 dimethylation (H3K9me2) is a highly conserved silencing epigenetic mark. Chromatin marked with H3K9me2 forms large domains in mammalian cells and overlaps well with lamina-associated domains and the B compartment defined by Hi-C. However, the role of H3K9me2 in 3-dimensional (3D) genome organization remains unclear. We investigated genome-wide H3K9me2 distribution, transcriptome, and 3D genome organization in mouse embryonic stem cells following the inhibition or depletion of five H3K9 methyltransferases (MTases): G9a, GLP, SETDB1, SUV39H1, and SUV39H2. H3K9me2 was regulated by all five MTases; however, H3K9me2 and transcription in the A and B compartments were regulated by different MTases. H3K9me2 in A compartments was primarily regulated by G9a/GLP and SETDB1, while H3K9me2 in the B compartments was regulated by all five MTases. Furthermore, decreased H3K9me2 correlated with changes to the more active compartmental state that accompanied transcriptional activation.
2021-03-18 | GSE169103 | GEO
Project description:The arginine or lysine methylation status of histones dynamically changes during many essential cellular processes, particularly during embryonic and hematopoietic stem cell development. The enzymes demethylate methyllysine residues have been well defined, but the enzymes demethylate the methylarginine residues during different cellular processes are unknown. In current study, we demonstrate that JMJD1B is a lysine demethylase for H3K9me2 and an arginine demethylase for H4R3me2s. To reveal the biological significance of JMJD1B as an arginine demethylase, we isolate hematopoietic stem/progenitor cells (HSPC) from wild-type and JMJD1B knockout (JKO) bone marrow. We then conduct ChIP-seq on H4R3me2s and H3K9me2 histone markers and perform RNA-seq to determine the global gene expression profiles. We have observed global demethylation of H4R3me2s at the gene body but not the intergenic regions in hematopoietic stem/progenitor cells. H4R3me2s demethylation at the gene body region is directly correlated with gene expression in these cells. Furthermore, knockout of JMJD1B causes defects in removing the H4R3me2s epigenetic marker, leading to down-regulation of genes important for blood cells differentiation and development. Altogether, our current study demonstrates that arginine demethylases exist in cellular systems and that JMJD1B demethylates H4R3me2s for proper epigenetic programming during development.
2018-03-14 | GSE94966 | GEO