The role of DNMT3A and TET1 in regulating promoter epigenetic landscapes
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393520 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5812850_1.fastq.gz | Fastqsanger.gz | |||
| SRR5812850_2.fastq.gz | Fastqsanger.gz | |||
| SRR5812860_1.fastq.gz | Fastqsanger.gz | |||
| SRR5812860_2.fastq.gz | Fastqsanger.gz | |||
| SRR5812870_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 122 |
Similar Datasets
Project description:In order to assess Tet1 binding, we first generated a Flag tagged Tet1 ES cells and then knocked out Dnmt3a in the [WT, Tet1-Flag] cells. By Tet1 ChIP and Flag ChIP, we showed that Tet1 binding was complementary to Dnmt3a. And Tet1 binding was not affected or slightly increased at majority of its targets.
2018-05-16 | GSE100955 | GEO
Project description:BACKGROUND:DNA methylation is a heritable epigenetic mark, enabling stable but reversible gene repression. In mammalian cells, DNA methyltransferases (DNMTs) are responsible for modifying cytosine to 5-methylcytosine (5mC), which can be further oxidized by the TET dioxygenases to ultimately cause DNA demethylation. However, the genome-wide cooperation and functions of these two families of proteins, especially at large under-methylated regions, called canyons, remain largely unknown. RESULTS:Here we demonstrate that DNMT3A and TET1 function in a complementary and competitive manner in mouse embryonic stem cells to mediate proper epigenetic landscapes and gene expression. The longer isoform of DNMT3A, DNMT3A1, exhibits significant enrichment at distal promoters and canyon edges, but is excluded from proximal promoters and canyons where TET1 shows prominent binding. Deletion of Tet1 increases DNMT3A1 binding capacity at and around genes with wild-type TET1 binding. However, deletion of Dnmt3a has a minor effect on TET1 binding on chromatin, indicating that TET1 may limit DNA methylation partially by protecting its targets from DNMT3A and establishing boundaries for DNA methylation. Local CpG density may determine their complementary binding patterns and therefore that the methylation landscape is encoded in the DNA sequence. Furthermore, DNMT3A and TET1 impact histone modifications which in turn regulate gene expression. In particular, they regulate Polycomb Repressive Complex 2 (PRC2)-mediated H3K27me3 enrichment to constrain gene expression from bivalent promoters. CONCLUSIONS:We conclude that DNMT3A and TET1 regulate the epigenome and gene expression at specific targets via their functional interplay.
| S-EPMC6042404 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2018-05-16 | GSE100957 | GEO
Project description:Using ChIP-seq to assess changes of histone modifications in response to Dnmt3a or Tet1 deficiency.
2018-05-16 | GSE100953 | GEO
Project description:DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational âhotspotâ at Arg882 (DNMT3A-R882H) cooperates with constitutively activated RAS in transforming murine hematopoietic stem/progenitor cells (HSPCs) ex vivo and inducing acute leukemias in vivo. DNMT3A-R882H potentiates aberrant transactivation of âstemnessâ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. Mechanistically, R882-mutated DNMT3A directly binds to cis-regulatory elements of these genes and induces focal CpG hypomethylation reminiscent of what was seen in human leukemias bearing DNMT3A R882 mutation. Furthermore, DNMT3A-R882H induced DNA hypomethylation facilitates gene enhancer/promoter activation and recruitment of Dot1l-associated transcription elongation machineries. Inactivation of Dot1l represses DNMT3AR882H-mediated stem cell gene dysregulation and acute leukemogenicity. In this dataset, we provided H3K4me1, H3K27ac and H3K79me2 ChIP-seq profiling data showing effect of DNMT3A R882H mutation or WT expression on epigenetic landscapes of hematopoietic stem/progenitor cells with NRAS G12D co-transduction. ChIP-seq analysis of Lin- enriched hematopoietic stem/progenitor cells with retroviral infection of NRAS G12D alone (EV-RAS), DNMT3A R882H with NRAS G12D (RH-RAS) or DNMT3A WT with NRAS G12D (WT-RAS) 3 weeks post-transduction. Antibodies of H3K4me1, H3K27ac and H3K79me2 were used.
2016-06-23 | E-GEOD-71472 | biostudies-arrayexpress
Project description:During differentiation, neurons experience a reorganization of DNA modification patterns within their genomes. However, the mechanisms underlying this developmental patterning and its role in defining the neuronaÂÂl state are currently unclear. Here, we find that the dÂÂe novo DNA methyltransferase Dnmt3a is necessary for elevated levels of 5-hydroxymethylcytosine (5hmC), a derivative of 5-methylcytosine (5mC), in olfactory sensory neurons (OSNs). Through an analysis of genome-wide 5mC and 5hmC distributions in isolated OSNs, we find that Dnmt3a-dependent 5mC and 5hmC occurs within regions of high accessibility, neural enhancers, and the transcription start sites of transcribed genes. Its loss results in the global disruption of gene expression patterns, including the upregulation of silent genes, the downregulation of mOSN-expressed genes, and the alteration of odorant-induced transcriptional responses of immediate early genes. Together, these results demonstrate that Dnmt3a is necessary to define the neuronal transcriptional state and may be broadly involved in refining expression profiles within differentiated cells. To determine the contributions of Dnmt3a to the DNA modification and transcriptional landscapes of a post-mitotic neuronal population, we performed DNA immunoprecipitation (DIP-seq) using antibodies specific for 5mC and 5hmC and rRNA-depleted transcriptional profiling (RNA-seq) coupled to high-throughput sequencing using genomic DNA or RNA from FACS-isolated mature olfactory sensory neurons (mOSNs) from main olfactory epithelium (MOE) of Dnmt3a wildtype (WT), heterozygous-null (Het), or homozygous-null (KO) 3-week old mice. Similarly, to compare this information with other epigenetic features of the MOE, we performed H3K4me1 (WT), H3K27ac (WT), and H3K27me3 (WT and KO) chromatin immunoprecipitation (ChIP)-seq and DNase I hypersensitivity assays (DNase-seq) using MOE nuclei from 3-week old mice. In addition, we assayed the influence of Dnmt3a-deficiency on the induction of odorant-responsive genes by exposing 3-week old Dnmt3a WT, Het, and KO mice to either water or a 1:1:1 mixture of amyl acetate:acetophenone:octanal for 1 hour and performed rRNA-depleted RNA-seq using RNA isolated from their MOEs.
2014-11-05 | E-GEOD-52464 | biostudies-arrayexpress
Project description:Inferring causal relationship between epigenetic marks and gene expression requires molecular tools which can precisely modify specific genomic regions in a living cell. In this work, we present a comprehensive, modular and extensible CRISPR/dCas9-based molecular toolbox for targeted epigenetic modulation and direct gene regulation. It features a system for expression of orthogonal dCas9 proteins fused to catalytic domains of various effectors, and includes a multi-gRNA system for targeting dCas9 orthologs to up to six loci. This part of the study aimed to determine the impact of promoter strength on modulating on- and off-target activity of dSpCas9-DNMT3A and dSpCas9-TET1 fusion proteins. The dSpCas9-DNMT3A N-terminal fusion was used to target IL6ST with four sgRNAs, and the dSpCas9-TET1 N-terminal fusion was used to target MGAT3 with five gRNAs. For each locus, two types of constructs were used: i) construct having both the fusion protein and the selection marker (PuroR) under the same strong, constitutive CAG promoter; ii) the fusion construct under the weak EFS promoter, while maintaining efficient selection of transfected cells with PuroR under the strong SV40 promoter. Epigenome-wide profiling was conducted using the Illumina Infinium Human MethylationEPIC Beadchip arrays to assess on- and off-target activity of the fusion proteins in transfected HEK293 cells.
2019-09-12 | GSE126528 | GEO
Project description:Using ChIP-seq to assess changes of histone modifications in response to Dnmt3a or Tet1 deficiency.
2018-05-16 | GSE112311 | GEO
Project description:TET1 maintains hypomethylation at bivalent promoters through its catalytic activity in embryonic stem cells (ESCs). However, whether and how TET1 exerts catalytic activity-independent functions in regulating bivalent genes is not well understood. Therefore, we mapped the TET1 interactome in mouse ESCs using a SILAC IP-MS proteomics approach.
2022-06-10 | PXD033587 | Pride
Project description:DNA Methyltransferase 3A (DNMT3A) is frequently mutated in various hematopoietic malignancies; however, the underlying oncogenic mechanisms remain elusive. Here, we report that DNMT3A mutational ‘hotspot’ at Arg882 (DNMT3A-R882H) cooperates with constitutively activated RAS in transforming murine hematopoietic stem/progenitor cells (HSPCs) ex vivo and inducing acute leukemias in vivo. DNMT3A-R882H potentiates aberrant transactivation of ‘stemness’ gene expression programs, notably transcription factors Meis1, Hox-A, Mn1 and Mycn. Mechanistically, R882-mutated DNMT3A directly binds to cis-regulatory elements of these genes and induces focal CpG hypomethylation reminiscent of what was seen in human leukemias bearing DNMT3A R882 mutation. Furthermore, DNMT3A-R882H induced DNA hypomethylation facilitates gene enhancer/promoter activation and recruitment of Dot1l-associated transcription elongation machineries. Inactivation of Dot1l represses DNMT3AR882H-mediated stem cell gene dysregulation and acute leukemogenicity. In this dataset, we provided H3K4me1, H3K27ac and H3K79me2 ChIP-seq profiling data showing effect of DNMT3A R882H mutation or WT expression on epigenetic landscapes of hematopoietic stem/progenitor cells with NRAS G12D co-transduction.
2016-06-23 | GSE71472 | GEO