Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

G9a plays distinct roles in maintaining DNA methylation, retrotransposon silencing and chromatin looping

ABSTRACT: G9a is a lysine methyltransferase that regulates epigenetic modifications, transcription and genome organization. However, whether these properties are dependent on one another or represent distinct functions of G9a remains unclear. In this study, we observe widespread DNA methylation loss in G9a depleted and catalytic mutant embryonic stem cells. Furthermore, we define how G9a regulates chromatin accessibility, epigenetic modifications and transcriptional silencing in both catalytic dependent and independent manners. Reactivated retrotransposons provide alternative promoters and splice sites leading to upregulation of neighboring genes and production of chimeric transcripts. Moreover, while topologically associated domains and compartments A/B definitions are largely unaffected, the loss of G9a leads to altered chromatin states, aberrant CTCF and cohesin binding, and differential chromatin looping especially at retrotransposons. Taken together, our findings reveal how G9a regulates the epigenome, transcriptome and higher-order chromatin structures in distinct mechanisms.

ORGANISM(S): Mus musculus

PROVIDER: GSE138102 | GEO | 2020/10/26

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

G9a plays distinct roles in maintaining DNA methylation, retrotransposon silencing and chromatin looping

Project description:G9a plays distinct roles in maintaining DNA methylation, retrotransposon silencing and chromatin looping

| PRJNA574621 | ENA

Dynamics of de novo heterochromatin assembly and disassembly at replication forks ensures fork stability

Project description:Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here, we discover a checkpoint regulated cascade of chromatin signaling that activates 5 the histone methyltransferase EHMT2/G9a to catalyze heterochromatin assembly at stressed replication forks. Using biochemical and single molecule chromatin fiber approaches, we show that G9a together with SUV39h1 induces chromatin compaction by accumulating the repressive modifications, H3K9me1/me2/me3, in the vicinity of stressed replication forks. This closed conformation is also favored by the G9a-dependent exclusion of the H3K9-demethylase 10 JMJD1A/KDM3A, which facilitates heterochromatin disassembly upon fork restart. Untimely heterochromatin disassembly from stressed forks by KDM3A enables PRIMPOL access, triggering ssDNA gap formation and sensitizing cells towards chemotherapeutic drugs. These findings may help explaining chemotherapy resistance and poor prognosis observed in cancer patients displaying elevated level of G9a/H3K9me3.

2023-05-12 | PXD041742 | Pride

H3K9me3 abcam.D.mel 3rd Instar Larvae Nuclei G9a mutant.Affy 2

Project description:modENCODE_submission_5611 This submission comes from a modENCODE project of Gary Karpen. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We aim to determine the locations of the major histone modifications across the Drosophila melanogaster genome. The modifications under study are involved in basic chromosomal functions such as DNA replication, gene expression, gene silencing, and inheritance. We will perform Chromatin ImmunoPrecipitation (ChIP) using genomic tiling arrays. We will initially assay localizations using chromatin from three cell lines and two embryonic stages, and will then extend the analysis of a subset of proteins to four additional animal tissues/stages. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Strain: G9a mutant (official name : G9a mutant genotype : G9a[RG5]/G9a[RG5] outcross : 3 transgene : n/a tags : homologous recombination tag : none description : Mutation generated by end-out homologous recombination at the G9a locus. The entire open reading frame of G9a has been removed. Developmental Stage: 3rd Instar Larvae; Genotype: G9a[RG5]/G9a[RG5]; Transgene: n/a; NUMBER OF REPLICATES: 4; EXPERIMENTAL FACTORS: Strain G9a mutant (official name : G9a mutant genotype : G9a[RG5]/G9a[RG5] outcross : 3 transgene : n/a tags : homologous recombination tag : none description : Mutation generated by end-out homologous recombination at the G9a locus. The entire open reading frame of G9a has been removed. Antibody H3K9me3 abcam (target is H3K9me3); Developmental Stage 3rd Instar Larvae

2013-03-13 | E-GEOD-45102 | biostudies-arrayexpress

HP1 wa191.D.mel 3rd Instar Larvae Nuclei G9a mutant.Affy 2

Project description:modENCODE_submission_5572 This submission comes from a modENCODE project of Gary Karpen. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We aim to determine the locations of the major histone modifications across the Drosophila melanogaster genome. The modifications under study are involved in basic chromosomal functions such as DNA replication, gene expression, gene silencing, and inheritance. We will perform Chromatin ImmunoPrecipitation (ChIP) using genomic tiling arrays. We will initially assay localizations using chromatin from three cell lines and two embryonic stages, and will then extend the analysis of a subset of proteins to four additional animal tissues/stages. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Strain: G9a mutant (official name : G9a mutant genotype : G9a[RG5]/G9a[RG5] outcross : 3 transgene : n/a tags : homologous recombination tag : none description : Mutation generated by end-out homologous recombination at the G9a locus. The entire open reading frame of G9a has been removed. Developmental Stage: 3rd Instar Larvae; Genotype: G9a[RG5]/G9a[RG5]; Transgene: n/a; NUMBER OF REPLICATES: 4; EXPERIMENTAL FACTORS: Strain G9a mutant (official name : G9a mutant genotype : G9a[RG5]/G9a[RG5] outcross : 3 transgene : n/a tags : homologous recombination tag : none description : Mutation generated by end-out homologous recombination at the G9a locus. The entire open reading frame of G9a has been removed. Antibody HP1 wa191 (target is HP1a); Developmental Stage 3rd Instar Larvae

2013-03-06 | E-GEOD-44885 | biostudies-arrayexpress

H3K36me3 abcam.D.mel 3rd Instar Larvae Nuclei G9a mutant.Affy 2

Project description:modENCODE_submission_5615 This submission comes from a modENCODE project of Gary Karpen. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We aim to determine the locations of the major histone modifications across the Drosophila melanogaster genome. The modifications under study are involved in basic chromosomal functions such as DNA replication, gene expression, gene silencing, and inheritance. We will perform Chromatin ImmunoPrecipitation (ChIP) using genomic tiling arrays. We will initially assay localizations using chromatin from three cell lines and two embryonic stages, and will then extend the analysis of a subset of proteins to four additional animal tissues/stages. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Strain: G9a mutant (official name : G9a mutant genotype : G9a[RG5]/G9a[RG5] outcross : 3 transgene : n/a tags : homologous recombination tag : none description : Mutation generated by end-out homologous recombination at the G9a locus. The entire open reading frame of G9a has been removed. Developmental Stage: 3rd Instar Larvae; Genotype: G9a[RG5]/G9a[RG5]; Transgene: n/a; NUMBER OF REPLICATES: 4; EXPERIMENTAL FACTORS: Strain G9a mutant (official name : G9a mutant genotype : G9a[RG5]/G9a[RG5] outcross : 3 transgene : n/a tags : homologous recombination tag : none description : Mutation generated by end-out homologous recombination at the G9a locus. The entire open reading frame of G9a has been removed. Antibody H3K36me3 abcam (target is H3K36me3); Developmental Stage 3rd Instar Larvae

2013-03-06 | E-GEOD-44894 | biostudies-arrayexpress

H3K9 methyltransferase G9a negatively regulates UHRF1 transdcription during leukemia cell differentiation.

Project description:Posttranslational modifications of histone N-terminal tails influence the status of chromatin and eventually control the transcriptional outcome of a particular gene. As a histone H3K9 methyltransferase (HMTase) in higher eukaryotes, G9a-mediated transcriptional repression is the major epigenetic silencing machinery. UHRF1 (ubiquitin-like with PHD and ring finger domains I) binds to hemi-methylated DNA and plays essential role in maintenance of DNA methylation by recruiting DNMT1. Here, we provide evidence that UHRF1 is transcriptionally downregulated by H3K9 HMTase G9a. We found that increased expression of G9a along with transcription factor YY1 specifically represses UHRF1 transcription. We uncovered showed that G9a regulates UHRF1-mediated H3K23 ubiquitylation and proper DNA replication maintenance by FACS analysis and propose that H3K9 HMTase G9a is a specific epigenetic regulator of UHRF1.

2018-12-31 | GSE63149 | GEO

A role for Widely Interspaced Zinc finger (WIZ) in retention of the G9a methyltransferase on chromatin

Project description:G9a and GLP lysine methyltransferases form a heterodimeric complex that is responsible for the bulk of cellular mono- and di-methylation on histone H3 lysine 9 (H3K9me1/me2). Widely Interspaced Zinc finger (WIZ) associates with the G9a/GLP protein complex, but its role in lysine methylation is poorly defined. Here, we show that WIZ regulates global H3K9me2 levels through a mechanism that involves retention of G9a on chromatin. We also show that WIZ-mediated chromatin loss of G9a/GLP results in altered gene expression and protein-protein interactions that are distinguishable from that of using a molecule-induced enzymatic inhibitor towards G9a/GLP – thus providing evidence that the G9a/GLP/WIZ complex has unique functions when bound to chromatin that are independent of the H3K9me2 mark DMSO, UNC0638, NS, and siWIZ treatments to HEK293T cells, assessing G9a and H3K9me2 localization, each performed in duplicate, plus one input control for each cell condition. 30 samples total.

2015-09-03 | E-GEOD-67317 | biostudies-arrayexpress

H3K9me2-Ab2 (new lot 3).D.mel 3rd Instar Larvae Nuclei G9a mutant.Affy 2

Project description:modENCODE_submission_5618 This submission comes from a modENCODE project of Gary Karpen. For full list of modENCODE projects, see http://www.genome.gov/26524648 Project Goal: We aim to determine the locations of the major histone modifications across the Drosophila melanogaster genome. The modifications under study are involved in basic chromosomal functions such as DNA replication, gene expression, gene silencing, and inheritance. We will perform Chromatin ImmunoPrecipitation (ChIP) using genomic tiling arrays. We will initially assay localizations using chromatin from three cell lines and two embryonic stages, and will then extend the analysis of a subset of proteins to four additional animal tissues/stages. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf EXPERIMENT TYPE: CHIP-chip. BIOLOGICAL SOURCE: Strain: G9a mutant (official name : G9a mutant genotype : G9a[RG5]/G9a[RG5] outcross : 3 transgene : n/a tags : homologous recombination tag : none description : Mutation generated by end-out homologous recombination at the G9a locus. The entire open reading frame of G9a has been removed. Developmental Stage: 3rd Instar Larvae; Genotype: G9a[RG5]/G9a[RG5]; Transgene: n/a; NUMBER OF REPLICATES: 4; EXPERIMENTAL FACTORS: Strain G9a mutant (official name : G9a mutant genotype : G9a[RG5]/G9a[RG5] outcross : 3 transgene : n/a tags : homologous recombination tag : none description : Mutation generated by end-out homologous recombination at the G9a locus. The entire open reading frame of G9a has been removed. Antibody H3K9me2-Ab2 (new lot 3) (target is H3K9me2); Developmental Stage 3rd Instar Larvae

2013-03-13 | E-GEOD-45105 | biostudies-arrayexpress

Proteomic analyses identify a novel role for EZH2 in the initiation of cancer cell drug tolerance

Project description:Acquisition of drug resistance remains a chief impediment to successful cancer therapy, and we previously described a transient drug-tolerant cancer cell population (DTPs) whose survival is in part dependent on the activities of the histone methyltransferases G9a/EHMT2 and EZH2, the latter being the catalytic component of the polycomb repressive complex 2 (PRC2). Here, we applied multiple proteomic techniques to better understand the role of these HMTs in the establishment of the DTP state. Proteome-wide comparisons of lysine methylation patterns revealed that DTPs have increased methylation on K116 of PRC member Jarid2, an event that helps stabilize and recruit PRC2 to chromatin. We also found that EZH2, in addition to methylating histone H3K27, also methylates G9a at K185, and that methylated G9a better recruits repressive complexes to chromatin; similar to complexes recruited by histone H3 methylated at K9. Finally, a detailed histone posttranslational modification (PTM) analysis shows that EZH2, either directly or through its ability to methylate G9a, alters H3K9 methylation in the specific context of H3 serine10 phosphorylation, and primarily in a cancer cell subpopulation that serves as DTP precursors. We also show that combinations of histone PTMs recruit a different set of complexes to chromatin, shedding light on the temporal mechanisms that contribute to drug tolerance.

2020-01-24 | MSV000084838 | MassIVE

A role for Widely Interspaced Zinc finger (WIZ) in retention of the G9a methyltransferase on chromatin

2015-09-03 | GSE67317 | GEO