Similar Datasets
Project description:Patterning of DNA methylation in eukaryotic genomes is controlled by de novo methylation, maintenance mechanisms and demethylation pathways. In Arabidopsis thaliana, DNA demethylation enzymes are clearly important for shaping methylation patterns, but how they are regulated is poorly understood. Here we show that the targeting of histone H3 lysine four trimethylation (H3K4me3) with the catalytic domain of the SDG2 histone methyltransferase potently erased DNA methylation and gene silencing at FWA and also erased CG DNA methylation in many other regions of the Arabidopsis genome. This methylation erasure was completely blocked in the ros1 dml2 dml3 triple mutant lacking DNA demethylation enzymes, showing that H3K4me3 promotes the active removal of DNA methylation. Conversely, we found that the targeted removal of H3K4me3 increased the efficiency of targeted DNA methylation. These results highlight H3K4me3 as a potent anti-DNA methylation mark and also pave the way for development of more powerful epigenome engineering tools.
| S-EPMC11842272 | biostudies-literature
Project description:Patterning of DNA methylation in eukaryotic genomes is shaped by de novo methylation, maintenance mechanisms, and demethylation pathways, but how these processes interface with epigenetic modification of histones is poorly understood. We found that the targeting of histone H3 lysine four trimethylation (H3K4me3) with the catalytic domain of the SDG2 histone methyltransferase potently erased DNA methylation and gene silencing at FWA and other genes, and also erased CG DNA methylation in the transcribed region of genes. This methylation erasure was completely blocked in the ros1 dml2 dml3 triple mutant which eliminates DNA demethylation enzymes, showing that H3K4me3 promotes the active removal of DNA methylation rather than preventing CG methylation maintenance. We also found that targeting the removal of H3K4me3 with the novel protein TRBIP1, which acts in part by recruiting the H3K4me3 demethylase JMJ14, causes potent gene silencing. Furthermore, using a CRISPR-based system to simultaneously target both TRBIP1 and a CG specific DNA methyltransferase, we observed more potent establishment of DNA methylation and gene silencing than targeting the DNA methyltransferase by itself. These results highlight H3K4me3 as a potent anti-DNA methylation mark, and reveal potent and specific tools for epigenome engineering.
2025-01-13 | GSE245959 | GEO
Project description:Patterning of DNA methylation in eukaryotic genomes is shaped by de novo methylation, maintenance mechanisms, and demethylation pathways, but how these processes interface with epigenetic modification of histones is poorly understood. We found that the targeting of histone H3 lysine four trimethylation (H3K4me3) with the catalytic domain of the SDG2 histone methyltransferase potently erased DNA methylation and gene silencing at FWA and other genes, and also erased CG DNA methylation in the transcribed region of genes. This methylation erasure was completely blocked in the ros1 dml2 dml3 triple mutant which eliminates DNA demethylation enzymes, showing that H3K4me3 promotes the active removal of DNA methylation rather than preventing CG methylation maintenance. We also found that targeting the removal of H3K4me3 with the novel protein TRBIP1, which acts in part by recruiting the H3K4me3 demethylase JMJ14, causes potent gene silencing. Furthermore, using a CRISPR-based system to simultaneously target both TRBIP1 and a CG specific DNA methyltransferase, we observed more potent establishment of DNA methylation and gene silencing than targeting the DNA methyltransferase by itself. These results highlight H3K4me3 as a potent anti-DNA methylation mark, and reveal potent and specific tools for epigenome engineering.
2025-01-13 | GSE245958 | GEO
Project description:This study investigates the mechanism by which histone deacetylase (HDAC) inhibitors up-regulate histone H3 lysine 4 (H3K4) methylation. Exposure of LNCaP prostate cancer cells and the prostate tissue of transgenic adenocarcinoma of the mouse prostate mice to the pan- and class I HDAC inhibitors (S)-(+)-N-hydroxy-4-(3-methyl-2-phenyl-butyrylamino)-benzamide (AR42), N-(2-aminophenyl)-4-[N-(pyridine-3-yl-methoxycarbonyl)-aminomethyl]-benzamide (MS-275), and vorinostat led to differential increases in H3K4 methylation. Chromatin immunoprecipitation shows that this accumulation of methylated H3K4 occurred in conjunction with decreases in the amount of the H3K4 demethylase RBP2 at the promoter of genes associated with tumor suppression and differentiation, including KLF4 and E-cadherin. This finding, together with the HDAC inhibitor-induced up-regulation of KLF4 and E-cadherin, suggests that HDAC inhibitors could activate the expression of these genes through changes in histone methylation status. Evidence indicates that this up-regulation of H3K4 methylation was attributable to the suppressive effect of these HDAC inhibitors on the expression of RBP2 and other JARID1 family histone demethylases, including PLU-1, SMCX, and LSD1, via the down-regulation of Sp1 expression. Moreover, shRNA-mediated silencing of the class I HDAC isozymes 1, 2, 3, and 8, but not that of the class II isozyme HDAC6, mimicked the drug effects on H3K4 methylation and H3K4 demethylases, which could be reversed by ectopic Sp1 expression. These data suggest a cross-talk mechanism between HDACs and H3K4 demethylases via Sp1-mediated transcriptional regulation, which underlies the complexity of the functional role of HDACs in the regulation of histone modifications.
| S-EPMC3014276 | biostudies-literature
Project description:Histone H3 lysine 4 methylation recruits DNA demethylases to enforce gene expression in Arabidopsis
| PRJNA1030744 | ENA
Project description:We propose a model for heterochromatin assembly that links DNA methylation with histone methylation and DNA replication. The hypomethylated Arabidopsis mutants ddm1 and met1 were used to investigate the relationship between DNA methylation and chromatin organization. Both mutants show a reduction of heterochromatin due to dispersion of pericentromeric low-copy sequences away from heterochromatic chromocenters. DDM1 and MET1 control heterochromatin assembly at chromocenters by their influence on DNA maintenance (CpG) methylation and subsequent methylation of histone H3 lysine 9. In addition, DDM1 is required for deacetylation of histone H4 lysine 16. Analysis of F(1) hybrids between wild-type and hypomethylated mutants revealed that DNA methylation is epigenetically inherited and represents the genomic imprint that is required to maintain pericentromeric heterochromatin.
| S-EPMC136960 | biostudies-literature
Project description:Patterning of DNA methylation in eukaryotic genomes is shaped by de novo methylation, maintenance mechanisms, and demethylation pathways, but how these processes interface with epigenetic modification of histones is poorly understood. We found that the targeting of histone H3 lysine four trimethylation (H3K4me3) with the catalytic domain of the SDG2 histone methyltransferase potently erased DNA methylation and gene silencing at FWA and other genes, and also erased CG DNA methylation in the transcribed region of genes. This methylation erasure was completely blocked in the ros1 dml2 dml3 triple mutant which eliminates DNA demethylation enzymes, showing that H3K4me3 promotes the active removal of DNA methylation rather than preventing CG methylation maintenance. We also found that targeting the removal of H3K4me3 with the novel protein TRBIP1, which acts in part by recruiting the H3K4me3 demethylase JMJ14, causes potent gene silencing. Furthermore, using a CRISPR-based system to simultaneously target both TRBIP1 and a CG specific DNA methyltransferase, we observed more potent establishment of DNA methylation and gene silencing than targeting the DNA methyltransferase by itself. These results highlight H3K4me3 as a potent anti-DNA methylation mark, and reveal potent and specific tools for epigenome engineering.
2025-01-13 | GSE245960 | GEO
Project description:Methylation of histone H3 lysine 9 (H3K9) is a hallmark of transcriptional silencing in many organisms. In Arabidopsis thaliana, dimethylation of H3K9 (H3K9m2) is important in the silencing of transposons and in the control of DNA methylation. We constructed a high-resolution genome-wide map of H3K9m2 methylation by using chromatin immunoprecipitation coupled with whole genome Roche Nimblegen microarrays (ChIP-chip). We observed a very high coincidence between H3K9m2 and CHG methylation (where H is either A,T or C) throughout the genome. The coding regions of genes that are associated exclusively with methylation in a CG context did not contain H3K9m2. In addition, we observed two distinct patterns of H3K9m2. Transposons and other repeat elements present in the euchromatic arms contained small islands of H3K9m2 present at relatively low levels. In contrast, pericentromeric/centromeric regions of Arabidopsis chromosomes contained long, rarely interrupted blocks of H3K9m2 present at much higher average levels than seen in the chromosome arms. These results suggest a complex interplay between H3K9m2 and different types of DNA methylation and suggest that distinct mechanisms control H3K9m2 in different compartments of the genome.
| S-EPMC2522283 | biostudies-literature
Project description:FLOWERING LOCUS T (FT) plays a key role as a mobile floral induction signal that initiates the floral transition. Therefore, precise control of FT expression is critical for the reproductive success of flowering plants. Coexistence of bivalent histone H3 lysine 27 trimethylation (H3K27me3) and H3K4me3 marks at the FT locus and the role of H3K27me3 as a strong FT repression mechanism in Arabidopsis have been reported. However, the role of an active mark, H3K4me3, in FT regulation has not been addressed, nor have the components affecting this mark been identified. Mutations in Arabidopsis thaliana Jumonji4 (AtJmj4) and EARLY FLOWERING6 (ELF6), two Arabidopsis genes encoding Jumonji (Jmj) family proteins, caused FT-dependent, additive early flowering correlated with increased expression of FT mRNA and increased H3K4me3 levels within FT chromatin. Purified recombinant AtJmj4 protein possesses specific demethylase activity for mono-, di-, and trimethylated H3K4. Tagged AtJmj4 and ELF6 proteins associate directly with the FT transcription initiation region, a region where the H3K4me3 levels were increased most significantly in the mutants. Thus, our study demonstrates the roles of AtJmj4 and ELF6 as H3K4 demethylases directly repressing FT chromatin and preventing precocious flowering in Arabidopsis.
| S-EPMC2777508 | biostudies-other
Project description:The dynamic regulation of chromatin structure by histone post-translational modification is an essential regulatory mechanism that controls global gene transcription. The Kdm4 family of H3K9me2,3 and H3K36me2,3 dual specific histone demethylases has been implicated in development and tumorigenesis. Here we show that Drosophila Kdm4A and Kdm4B are together essential for mediating ecdysteroid hormone signaling during larval development. Loss of Kdm4 genes leads to globally elevated levels of the heterochromatin marker H3K9me2,3 and impedes transcriptional activation of ecdysone response genes, resulting in developmental arrest. We further show that Kdm4A interacts with the Ecdysone Receptor (EcR) and colocalizes with EcR at its target gene promoter. Our studies suggest that Kdm4A may function as a transcriptional co-activator by removing the repressive histone mark H3K9me2,3 from cognate promoters.
| S-EPMC3792421 | biostudies-literature