Genes regulated by SET7/9 knockdown in gastric cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE59834 | GEO | 2015/07/24
SECONDARY ACCESSION(S): PRJNA256323
REPOSITORIES: GEO
Similar Datasets
Project description:Expression of SET7/9, a histone methyltransferase, was frequently reduced in cultured and primary gastric cancers. To identify the SET7/9 target genes in gastric cancer, we performed siRNA-based knockdown of SET7/9 in MKN74 and MKN45 cells and then examined significant expression changes of genes by microarray. Transfection of SET7/9 siRNA into MKN74 and MKN45 cells were performed by electroporation. After 48hrs, cells were harvested. Total RNA was used for cDNA microarray.
2015-07-24 | E-GEOD-59834 | biostudies-arrayexpress
Project description:We analyzed the role of the histone lysine methyltransferase Set7/9 in the differentiation of human embryonic stem (ES) cells. Human ES cell lines expressing a control short hairpin and a short hairpin against Set7/9 were established and the genome wide expression profile was compared between both cell lines at different days during differentiation. Analysis of both profiles indicates that in the absence of Set7/9 there is a delay in the silencing of self-renewal factors as well as in the induction of differentiation markers. These results indicate that Set7/9 plays an active role in the differentiation of human ES cells. control and set7/9 shRNA hESCs were differentiated, and profiling was realized at days 0, 8 and 15.
2016-02-17 | E-GEOD-24768 | biostudies-arrayexpress
Project description:SET7 is a histone methyltransferase suggested to influence gene expression by modifying local chromatin at H3K4me1. RNA-sequencing experiment aimed at identifying the genes regulated by SET7 in MDA-MB-231 cells after SET7 repression. Then comparing the results with those obtained from RNA-seq data after ERRα inactivation (GSE49110) allowed to identify genes regulated by ERRα and SET7.
2021-06-09 | GSE163017 | GEO
Project description:We analyzed the role of the histone lysine methyltransferase Set7/9 in the differentiation of human embryonic stem (ES) cells. Human ES cell lines expressing a control short hairpin and a short hairpin against Set7/9 were established and the genome wide expression profile was compared between both cell lines at different days during differentiation. Analysis of both profiles indicates that in the absence of Set7/9 there is a delay in the silencing of self-renewal factors as well as in the induction of differentiation markers. These results indicate that Set7/9 plays an active role in the differentiation of human ES cells.
2016-02-17 | GSE24768 | GEO
Project description:Fucoidan is a high-molecular polysaccharide whose main constituent is sulfated fucose. Extensive studies have demonstrated numerous interesting biological activities for fucoidan. We specifically focused on the anti-proliferation activity of fucoidan and examined the underlying mechanism in MKN45 gastric cancer cells. BrdU assay revealed that fucoidan impeded the MKN45 cell cycle by approximately 50%, and clonogenic assay also showed that fucoidan inhibited cell proliferation. Preliminary examinations of fucoidan using LDH assay showed no immediate cytotoxic effects at 24-h exposure. However, longer time courses revealed inhibition of cell growth at 4 days in a dose-dependent manner. Microarray analysis in MKN45 cells treated with fucoidan identified genes that were upregulated and downregulated in response to fucoidan, including MAP3K5, or ASK1 (apoptosis signal-regulating kinase), which was upregulated by 1.38-fold. Western blot confirmed that fucoidan increased ASK1 protein levels, while reducing the levels of phosphorylated ASK1. Reduction of ASK1 by siRNA decreased proliferation of MKN45 cells. Our findings show that fucoidan may suppress cellular proliferation and DNA synthesis in MKN45 cells by suppressing the ASK1-p38 signaling pathway through reduction of phosphorylated ASK1 levels.
2017-02-09 | GSE58774 | GEO
Project description:Methyl-dependent regulation of transcription has expanded from a traditional focus on histones to encompass transcription factor modulation. While the Set7 lysine methyltransferase is associated with pro-inflammatory gene expression in vascular endothelial cells, genome-wide regulatory roles remain to be investigated. From initial characterization of Set7 as specific for methyl-lysine 4 of H3 histones (H3K4m1), biochemical activity toward non-histone substrates has revealed additional mechanisms of gene regulation. mRNA-Seq revealed transcriptional deregulation of over 8,000 genes in an endothelial model of Set7 knockdown. Gene ontology identified up-regulated pathways involved in developmental processes and extracellular matrix remodeling, whereas pathways regulating the inflammatory response as well as nitric oxide signaling were down-regulated. Chromatin maps derived from ChIP-Seq profiling of H3K4m1 identified several hundred loci with loss of H3K4m1 at gene regulatory elements associated with an unexpectedly subtle effect on gene expression. Transcription factor network analysis implicated six previously described Set7 substrates in mRNA-Seq changes, and we predict that Set7 post-translationally regulates other transcription factors associated with vascular endothelial gene expression through the presence of Set7 amino acid methylation motifs. We describe a role for Set7 in regulating developmental pathways and response to stimuli (inflammation/immune response) in human endothelial cells of vascular origin. Set7-dependent gene expression changes that occurred independent of H3K4m1 may involve transcription factor lysine methylation events. The method of mapping measured transcriptional changes to transcription factors to identify putative substrates with strong associations to functional changes is applicable to substrate prediction for other broad-substrate histone modifiers.
2017-01-07 | GSE93236 | GEO
Project description:The Set7 methyltransferase regulates the expression of several genes through the methylation of histones and modulates the activity of non-histone proteins. However, the role of Set7 in cardiac remodeling and heart failure remains unknown. To address this question, wild type (WT) and Set7 knockout (KO) male mice were injected with isoproterenol (60 mg/kg) or saline subcutaneously for 14 days. WT mice injected with isoproterenol displayed a decrease in Set7 activity in the heart, although Set7 protein levels were unchanged. WT and Set7 KO mice injected with isoproterenol exhibited an increase in the heart weight and cardiomyocyte area compared to their respective controls. However, Set7 KO mice displayed an exacerbated cardiac hypertrophy in response to isoproterenol compared to WT mice. In addition, Set7 deletion attenuated isoproterenol-induced cardiac fibrosis. Echocardiograms revealed that WT mice injected with isoproterenol had lowered ejection fractions and fractional shortening, and increased E/A ratios compared to their controls. Conversely, Set7 KO mice did not show alteration in these parameters in response to isoproterenol. Both isoproterenol and Set7 deletion changed the transcriptional profile of the heart. Moreover, Set7 deletion increased the expression of mitochondrial biogenesis and antioxidant factors in the heart and reduced the expression of cellular senescence and inflammation markers. Taken together, our data suggest that Set7 deletion reduces isoproterenol-induced myocardial fibrosis and prevents heart failure, suggesting that Set7 plays an important role in cardiac remodeling and function.
2024-04-18 | GSE207581 | GEO
Project description:The ability of neural stem cells (NSCs) to switch between quiescence and proliferation is crucial for brain development and homeostasis. Increasing evidence suggest that variants of histone lysine methyltransferases including KMT5A are associated with neurodevelopmental disorders. However, the function of KMT5A/Pr-set7/SETD8 in the central nervous system is not well established. Here, we show that Drosophila Pr-Set7 is a novel regulator of NSC reactivation. Loss-of-function of pr-set7 causes a delay in NSC reactivation and loss of H4K20 monomethylation in the brain. Through NSC-specific in vivo profiling, we demonstrate that Pr-set7 binds to the promoter region of cyclin dependent kinase 1 (cdk1) and Wnt pathway transcriptional co-activator earthbound1/jerky (ebd1). Further validation indicates that Pr-set7 is required for the expression of cdk1 and ebd1 in the brain. Similar to Pr-set7, Cdk1 and Ebd1 promote NSC reactivation. Moreover, Cdk1 upregulates the Ebd1 levels in NSCs, while Ebd1 appears to downregulate Cdk1 expression, suggesting a negative feedback regulation. Finally, overexpression of Cdk1 and Ebd1 significantly suppressed NSC reactivation defects observed in pr-set7-depleted brains. Therefore, Pr-set7, the sole H4K20 methyltransferase, promotes NSC reactivation through regulating Wnt signaling and cell-cycle progression. Given the conservation of Pr-set7, our findings may contribute to the understanding of mammalian KMT5A/PR-SET7/SETD8 in NSC proliferation and associated neurodevelopmental disorders.
2021-02-09 | GSE158764 | GEO
Project description:Cellular senescence is an ireversible growth arrest with alterd metabolic potentials including DNA, RNA and protein dynamics. We found that loss of the SETD8/PR-Set7 methyltransferase, which catalyzes mono-methylation of histone H4 at lysine 20 (H4K20me1), induces senescence in human fibroblasts. To investigate the role of SETD8 in cellular senescence, we performed a microarray-based transcriptomic analysis in SETD8-knockdown cells. Our results demonstrate that SETD8 links the epigenomic gene regulation to senescence-associated metabolic remodeling.
2017-03-30 | GSE86545 | GEO
Project description:Yin Yang 1 (YY1) is a multifunctional transcription factor shown to be critical in a variety of biological processes. Although it has been reported to be regulated by multiple types of post-translational modifications (PTMs), whether YY1 is methylated, which enzyme methylates YY1, and hence the functional significance of YY1 methylation remain completely unknown. Here we reported the first methyltransferase, SET7/9 (KMT7), capable of methylating YY1 in vitro and in vivo at two highly conserved lysine (K) residues, K173 and K411, located in two distinct domains, one in the central glycine-rich region and the other in the very carboxyl-terminus. Functional study revealed that SET7/9-mediated YY1 methylation regulated YY1 DNA-binding activity both in vitro and at specific genomic loci in cultured cells. Consistently, SET7/9-mediated YY1 methylation was shown to involve in YY1-regulated gene transcription and cell proliferation. Our findings revealed a novel regulatory strategy, methylation by lysine methyltransferase, imposed on YY1 protein, and linked YY1 methylation with its biological functions.
2017-02-13 | GSE69758 | GEO