The impact of G9a-inhibitors in T-cell and Treg differentiation [RNA-Seq]
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE196226 | GEO | 2022/12/31
REPOSITORIES: GEO
Similar Datasets
Project description:As methyltransferase G9a has been implicated in immune cell differentiation we have assessed the role of G9a enzymatic inhibitors (UNC0642) in the differentiation of human naïve T-cells under different stimulation conditions.
2022-12-31 | GSE196903 | GEO
Project description:Epigenetic modifications modulate gene expression and, when deregulated, contribute to the development and progression of cancer. G9a (EHMT2) and EZH2 are two histone methyltransferases commonly upregulated in several cancer types, leading to the silencing of tumor suppressor genes. We performed high throughput sequencing of a breast cancer cell line (MDA-MB-231), an ovarian cancer cell line (CAOV3) and a melanoma cell line (D14) treated with a G9a inhibitor (UNC0642), EZH2 inhibitor (GSK126) and their combination.
2022-02-20 | GSE168763 | GEO
Project description:PPARγ promotes adipogenesis while Wnt proteins inhibit adipogenesis. However, the mechanisms that control expression of these positive and negative master regulators of adipogenesis remain incompletely understood. By genome-wide histone methylation profiling in preadipocytes, we find that among gene loci encoding adipogenesis regulators, histone methyltransferase (HMT) G9a-mediated repressive epigenetic mark H3K9me2 is enriched on the entire PPARγ locus. H3K9me2 and G9a levels decrease during adipogenesis, which correlates inversely with induction of PPARγ. Removal of H3K9me2 by G9a deletion enhances chromatin opening and binding of adipogenic transcription factor C/EBP-beta to PPARγ promoter, which promotes PPARγ expression. Interestingly, G9a represses PPARγ expression in an HMT activity-dependent manner but facilitates Wnt10a expression independent of its enzymatic activity. Consistently, deletion of G9a or inhibiting G9a HMT activity promotes adipogenesis. Finally, deletion of G9a in mouse adipose tissues increases adipogenic gene expression and tissue weight. Thus, by inhibiting PPARγ expression and facilitating Wnt10a expression, G9a represses adipogenesis. Examination of gene expression changes in G9a KO brown preadipocytes
2013-02-01 | E-GEOD-41456 | biostudies-arrayexpress
Project description:Purpose: The aim of this study is to compare brain transcriptome profile (RNA-seq) after G9a inhibition. Methods: Hippocampus profiles of 7-month-old SAMP8 Control and SAMP8 Treated mice groups were generated by deep sequencing, pooled using Ilumnia Hiseq. Results: G9a inhibition with UNC0642 induces a transcriptional profile that allows beneficial effects on cognitive performance. Differential expression analysis identified 697 differentially expressed genes (DEG) (fold change cutoff of ≥1.3, p-value<0.05). Of which 217 are reduced, and 480 are increased in SAMP8 UNC0642. Conclusions: Our study showed the first transcriptome analysis of whole brain after G9a inhibition, generated by RNA-seq technology, demonstrating transcriptomic changes.
2021-11-24 | GSE189249 | GEO
Project description:Purpose: The aim of this study is to compare brain transcriptome profile (RNA-seq) after G9a inhibition. Methods: Hippocampus profiles of 7-month-old SAMP8 Control and SAMP8 Treated mice groups were generated by deep sequencing, pooled using Ilumnia Hiseq. Results: G9a inhibition with UNC0642 induces a transcriptional profile that allows beneficial effects on cognitive performance. Differential expression analysis identified 697 differentially expressed genes (DEG) (fold change cutoff of ≥1.3, p-value<0.05). Of which 217 are reduced, and 480 are increased in SAMP8 UNC0642. Conclusions: Our study showed the first transcriptome analysis of whole brain after G9a inhibition, generated by RNA-seq technology, demonstrating transcriptomic changes.
2021-11-24 | GSE189248 | GEO
Project description:PPAR? promotes adipogenesis while Wnt proteins inhibit adipogenesis. However, the mechanisms that control expression of these positive and negative master regulators of adipogenesis remain incompletely understood. By genome-wide histone methylation profiling in preadipocytes, we find that among gene loci encoding adipogenesis regulators, histone methyltransferase (HMT) G9a-mediated repressive epigenetic mark H3K9me2 is enriched on the entire PPAR? locus. H3K9me2 and G9a levels decrease during adipogenesis, which correlates inversely with induction of PPAR?. Removal of H3K9me2 by G9a deletion enhances chromatin opening and binding of adipogenic transcription factor C/EBP-beta to PPAR? promoter, which promotes PPAR? expression. Interestingly, G9a represses PPAR? expression in an HMT activity-dependent manner but facilitates Wnt10a expression independent of its enzymatic activity. Consistently, deletion of G9a or inhibiting G9a HMT activity promotes adipogenesis. Finally, deletion of G9a in mouse adipose tissues increases adipogenic gene expression and tissue weight. Thus, by inhibiting PPAR? expression and facilitating Wnt10a expression, G9a represses adipogenesis. Examination of 3 different histone modification changes in 3T3-L1 preadipocytes
2013-02-01 | E-GEOD-41455 | biostudies-arrayexpress
Project description:We have investigated the role of the histone methyltransferase G9a in the establishment of silent nuclear compartments. Following conditional knockout of the G9a methyltransferase in mouse ESCs, 167 genes were significantly up-regulated, and no genes were strongly down-regulated. A partially overlapping set of 119 genes were up-regulated after differentiation of G9a-depleted cells to neural precursors. Promoters of these G9a-repressed genes were AT rich and H3K9me2 enriched but H3K4me3 depleted and were not highly DNA methylated. Representative genes were found to be close to the nuclear periphery, which was significantly enriched for G9a-dependent H3K9me2. Strikingly, although 73% of total genes were early replicating, more than 71% of G9a-repressed genes were late replicating, and a strong correlation was found between H3K9me2 and late replication. However, G9a loss did not significantly affect subnuclear position or replication timing of any non-pericentric regions of the genome, nor did it affect programmed changes in replication timing that accompany differentiation. We conclude that G9a is a gatekeeper for a specific set of genes localized within the late replicating nuclear periphery. 4 cell states each in duplicate (i.e. a total of 8 individual replicates)
2010-06-20 | E-GEOD-18076 | biostudies-arrayexpress
Project description:We have investigated the role of the histone methyltransferase G9a in the establishment of silent nuclear compartments. Following conditional knockout of the G9a methyltransferase in mouse ESCs, 167 genes were significantly up-regulated, and no genes were strongly down-regulated. A partially overlapping set of 119 genes were up-regulated after differentiation of G9a-depleted cells to neural precursors. Promoters of these G9a-repressed genes were AT rich and H3K9me2 enriched but H3K4me3 depleted and were not highly DNA methylated. Representative genes were found to be close to the nuclear periphery, which was significantly enriched for G9a-dependent H3K9me2. Strikingly, although 73% of total genes were early replicating, more than 71% of G9a-repressed genes were late replicating, and a strong correlation was found between H3K9me2 and late replication. However, G9a loss did not significantly affect subnuclear position or replication timing of any non-pericentric regions of the genome, nor did it affect programmed changes in replication timing that accompany differentiation. We conclude that G9a is a gatekeeper for a specific set of genes localized within the late replicating nuclear periphery. 4 cell states each in duplicate (i.e. a total of 8 individual replicates)
2009-11-02 | E-GEOD-18079 | biostudies-arrayexpress
Project description:The methyltransferase G9a was found to play a role in the disease progression of a murine model of AML. Mouse HSPCs were transformed with HoxA9/Meis1 and treated with G9a/GLP inhibitor UNC0638. We used microarrays to detail the global program of gene expression that depends on the methyltransferase activity of G9a in murine AML cells.
2014-01-08 | E-GEOD-53894 | biostudies-arrayexpress
Project description:We report a novel translation-regulatory function of G9a, a histone methyltransferase and well-understood transcriptional repressor, in promoting hyperinflammation and lymphopenia; two hallmarks of endotoxin tolerance (ET)-associated chronic inflammatory complications. Using multiple approaches, we demonstrate that G9a interacts with multiple translation regulators during ET, particularly the N6-methyladenosine (m6A) RNA methyltransferase METTL3, to co-upregulate expression of certain m6A-modified mRNAs that encode immune-checkpoint and anti-inflammatory proteins. Mechanistically, G9a promotes m6A methyltransferase activity of METTL3 at translational/post-translational level by regulating its expression, its methylation, and its cytosolic localization during ET. Additionally, from a broader view extended from the G9a-METTL3-m6A translation regulatory axis, our translatome proteomics approach identified numerous “G9a-translated” proteins that unite the networks associated with inflammation dysregulation, T cell dysfunction, and systemic cytokine response. In sum, we identified a previously unrecognized function of G9a in protein-specific translation that can be leveraged to treat ET-related chronic inflammatory diseases.
2023-10-20 | PXD044382 | Pride