Next Generation Sequencing of human trophoblast stem cells expressing a doxycycline-inducible dominant-negative MAML1 construct.
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE233140 | GEO | 2023/06/30
REPOSITORIES: GEO
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Project description:Glioblastoma multiforme (GBM) is the most malignant and most common tumor of the central nervous system characterized by rapid growth and extensive tissue infiltration. GBM results in more years of life lost than any other cancer type. Notch signaling has been implicated in GBM pathogenesis through several modes of action. Inhibition of Notch leads to a reduction of cancer-initiating cells in gliomas and reduces proliferation and migration. Deltex1 (DTX1) is part of an alternative Notch signaling pathway distinct from the canonical MAML1/RBPJκ-mediated cascade. In this study, we show that DTX1 activates both the RTK/PI3K/PKB as well as the MAPK/ERK pathway. Moreover, we found the anti-apoptotic factor Mcl-1 to be induced by DTX1. In accordance with this, the clonogenic potential and proliferation rates of glioma cell lines correlated with DTX1 levels. DTX1 knock down mitigated the tumorigenic potential in vivo, and overexpression of DTX1 increased cell migration and invasion of tumor cells accompanied by an elevation of the pro-migratory factors PKBβ and Snail1. Microarray gene expression analysis identified a DTX1-specific transcriptional program - including microRNA-21 - which is distinct from the canonical Notch signaling. We propose the alternative Notch pathway via DTX1 as oncogenic factor in malignant glioma and found low DTX1 expression levels to correlate with prolonged survival of GBM and early breast cancer patients in open source databases. We generated human glioma U373 cell lines stably expressing Enhanced Green Fluorescent Protein (EGFP), human Deltex1-Myc Tag (DTX1-myc), or Master Mind Like 1 - dominant negative (MAML1-dn) to compare differences in overall gene expression. We included 3x EGFP control samples, 3x DTX1-myc, and 3 MAML1-dn samples.
2012-05-31 | E-GEOD-22772 | biostudies-arrayexpress
Project description:Next Generation Sequencing of human trophoblast stem cells expressing a doxycycline-inducible dominant-negative MAML1 construct.
| PRJNA975111 | ENA
Project description:Mastermind-like 1 (MAML1) is a transcriptional coregulator that has been associated with early development of many systems such as neuronal, muscular, cardiovascular and urogenital. The present study aimed to explore the genome-wide effects of MAML1 on gene expression and DNA methylation in human embryonic kidney cells. RNA expression was measured using a microarray that screens approximately 36,000 transcripts, and DNA methylation was determined for 450,000 CpG sites. 225 genes were found to be differentially expressed, while 11802 CpG sites were found to be differentially methylated in MAML1-expressing cells. A subset of 211 differentially methylated loci was associated with the expression of 85 genes. Gene ontology analysis revealed that these genes are involved in the regulation of urogenital system development, cell adhesion and embryogenesis. The aim of the study was to identify genes regulated by mastermind-like pritein 1 and DNA methylation, using genome-wide approach. We assayed the effects of MAML1 overexpression, as well as knock-down, on global DNA methylation profiles in HEK293 cells. 11802 CpG sites were found to be differentially methylated in MAML1-overexpressing cells. However, no significant changes were observed by comparing HEK293_H_siControl with HEK293_H_siMAML1.
2014-10-08 | E-GEOD-62177 | biostudies-arrayexpress
Project description:Mastermind-like 1 (MAML1) is a transcriptional coregulator that has been associated with early development of many systems such as neuronal, muscular, cardiovascular and urogenital. The present study aimed to explore the genome-wide effects of MAML1 on gene expression and DNA methylation in human embryonic kidney cells. RNA expression was measured using a microarray that screens approximately 36,000 transcripts, and DNA methylation was determined for 450,000 CpG sites. 225 genes were found to be differentially expressed, while 11802 CpG sites were found to be differentially methylated in MAML1-expressing cells. A subset of 211 differentially methylated loci was associated with the expression of 85 genes. Gene ontology analysis revealed that these genes are involved in the regulation of urogenital system development, cell adhesion and embryogenesis. The aim of the study was to identify genes regulated by mastermind-like pritein 1 and DNA methylation, using genome-wide approach.
2014-10-08 | GSE62177 | GEO
Project description:Mastermind-like 1 (MAML1) is a transcriptional coregulator that has been associated with early development of many systems such as neuronal, muscular, cardiovascular and urogenital. The present study aimed to explore the genome-wide effects of MAML1 on gene expression and DNA methylation in human embryonic kidney cells. RNA expression was measured using a microarray that screens approximately 36,000 transcripts, and DNA methylation was determined for 450,000 CpG sites. 225 genes were found to be differentially expressed, while 11802 CpG sites were found to be differentially methylated in MAML1-expressing cells. A subset of 211 differentially methylated loci was associated with the expression of 85 genes. Gene ontology analysis revealed that these genes are involved in the regulation of urogenital system development, cell adhesion and embryogenesis. The aim of the study was to identify genes regulated by mastermind-like pritein 1 and DNA methylation, using genome-wide approach.
2014-10-08 | GSE62175 | GEO
Project description:Glioblastoma multiforme (GBM) is the most malignant and most common tumor of the central nervous system characterized by rapid growth and extensive tissue infiltration. GBM results in more years of life lost than any other cancer type. Notch signaling has been implicated in GBM pathogenesis through several modes of action. Inhibition of Notch leads to a reduction of cancer-initiating cells in gliomas and reduces proliferation and migration. Deltex1 (DTX1) is part of an alternative Notch signaling pathway distinct from the canonical MAML1/RBPJκ-mediated cascade. In this study, we show that DTX1 activates both the RTK/PI3K/PKB as well as the MAPK/ERK pathway. Moreover, we found the anti-apoptotic factor Mcl-1 to be induced by DTX1. In accordance with this, the clonogenic potential and proliferation rates of glioma cell lines correlated with DTX1 levels. DTX1 knock down mitigated the tumorigenic potential in vivo, and overexpression of DTX1 increased cell migration and invasion of tumor cells accompanied by an elevation of the pro-migratory factors PKBβ and Snail1. Microarray gene expression analysis identified a DTX1-specific transcriptional program - including microRNA-21 - which is distinct from the canonical Notch signaling. We propose the alternative Notch pathway via DTX1 as oncogenic factor in malignant glioma and found low DTX1 expression levels to correlate with prolonged survival of GBM and early breast cancer patients in open source databases.
2012-06-01 | GSE22772 | GEO
Project description:Microvascular complications of diabetes are chronic diseases of small vessels. We previously found that CD4+ regulatory T-cells (Tregs) are markedly reduced in type 2 diabetes (T2D) after ischemic injury in both mice and humans, and that Treg deficiency in immunodeficient mice impairs vascular regeneration. However, the mechanisms by which Tregs protect against diabetic vascular disease remain unclear. Here, we demonstrate that endothelial cells (ECs) upregulate the transcription factor YY1 during post-ischemic vascular regeneration, but this response is blunted in diabetic ECs. Endothelial-specific deletion of YY1 leads to defective vascular regeneration following ischemia. Mechanistically, YY1 binds to the MAML1 promoter at regions enriched for H3K4me3 and H3K27ac. YY1 activates MAML1 transcription, likely by recruiting H3K4me3 writers (SETD1A, MLL1, MLL2) and their scaffold WDR5 within the COMPASS complex, together with the H3K27ac writer p300. Functionally, Tregs enhance vascular regeneration through paracrine signaling even in T2D mice. Adoptive Treg transfer restores regenerative capacity by reactivating the endothelial YY1/MAML1 axis. These findings identify a Treg-YY1-MAML1 pathway as a key regulator of endothelial function and vascular repair, offering mechanistic insight into how Tregs promote tissue regeneration in diabetes-associated microvascular dysfunction.
2026-05-18 | GSE331194 | GEO
Project description:Microvascular complications of diabetes are chronic diseases of small vessels. We previously found that CD4+ regulatory T-cells (Tregs) are markedly reduced in type 2 diabetes (T2D) after ischemic injury in both mice and humans, and that Treg deficiency in immunodeficient mice impairs vascular regeneration. However, the mechanisms by which Tregs protect against diabetic vascular disease remain unclear. Here, we demonstrate that endothelial cells (ECs) upregulate the transcription factor YY1 during post-ischemic vascular regeneration, but this response is blunted in diabetic ECs. Endothelial-specific deletion of YY1 leads to defective vascular regeneration following ischemia. Mechanistically, YY1 binds to the MAML1 promoter at regions enriched for H3K4me3 and H3K27ac. YY1 activates MAML1 transcription, likely by recruiting H3K4me3 writers (SETD1A, MLL1, MLL2) and their scaffold WDR5 within the COMPASS complex, together with the H3K27ac writer p300. Functionally, Tregs enhance vascular regeneration through paracrine signaling even in T2D mice. Adoptive Treg transfer restores regenerative capacity by reactivating the endothelial YY1/MAML1 axis. These findings identify a Treg-YY1-MAML1 pathway as a key regulator of endothelial function and vascular repair, offering mechanistic insight into how Tregs promote tissue regeneration in diabetes-associated microvascular dysfunction.
2026-05-18 | GSE331193 | GEO
Project description:Mastermind-like 1 (MAML1) is a transcriptional coregulator that has been associated with early development of many systems such as neuronal, muscular, cardiovascular and urogenital. The present study aimed to explore the genome-wide effects of MAML1 on gene expression and DNA methylation in human embryonic kidney cells. RNA expression was measured using a microarray that screens approximately 36,000 transcripts, and DNA methylation was determined for 450,000 CpG sites. 225 genes were found to be differentially expressed, while 11802 CpG sites were found to be differentially methylated in MAML1-expressing cells. A subset of 211 differentially methylated loci was associated with the expression of 85 genes. Gene ontology analysis revealed that these genes are involved in the regulation of urogenital system development, cell adhesion and embryogenesis. The aim of the study was to identify genes regulated by mastermind-like pritein 1 and DNA methylation, using genome-wide approach. We assayed the effects of MAML1 overexpression, as well as knock-down, on global gene expression profiles in HEK293 cells. We applied a filter of p < 0.01 for significantly modulated gene expression and at least a 1.5-fold change in mean differential expression. By comparing HEK293 (AW01-03_H average) with HEK293_MAML1 samples (AW04-06_MAML1 average), 225 genes were found to be differentially expressed. However, no significant changes were observed by comparing HEK293_H_siControl (AW13-14_H_siCtrl average) with HEK293_H_siMAML1 (AW15-16_siMAML1 average).
2014-10-08 | E-GEOD-62175 | biostudies-arrayexpress
Project description:IER5 is required for Notch-mediated induction of squamous cell differentiation [ChIP-seq RBPJ & MAML1]
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