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Mastermind-like protein 1 regulates DNA methylation and expression of early developmental gene clusters in human embryonic kidney cells (methylation)

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE62177 | GEO | 2014/10/08

SECONDARY ACCESSION(S): PRJNA263374

REPOSITORIES: GEO

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Mastermind-like protein 1 regulates DNA methylation and expression of early developmental gene clusters in human embryonic kidney cells (methylation)

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

Mastermind-like protein 1 regulates DNA methylation and expression of early developmental gene clusters in human embryonic kidney cells (expression)

2014-10-08 | GSE62175 | GEO

Mastermind-like protein 1 regulates DNA methylation and expression of early developmental gene clusters in human embryonic kidney cells (expression)

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

Next Generation Sequencing of human trophoblast stem cells expressing a doxycycline-inducible dominant-negative MAML1 construct.

Project description:Mastermind-like 1 (MAML1) functions as a co-activator in the NOTCH signaling pathway. A truncated version of its wild type form, the so-called dominant-negative MAML1 (DN-MAML1) , lacks the transactivation domains that are needed for stimulation of gene expression. The aim of the study was to characterize the effects of NOTCH signaling pathway inhibition in human trophoblast stem cells (TSCs) by overexpression of DN-MAML1.

2023-06-30 | GSE233140 | GEO

Coordination of neuron production in mouse and human cerebral cortex by the homolog of Drosophila Mastermind protein

Project description:The coordination of progenitor self-renewal, neuronal production and migration is essential to the normal development and evolution of the cerebral cortex. Numerous studies have shown that the Notch, Wnt/beta-catenin and Neurogenin pathways contribute separately to progenitor expansion, neurogenesis, and neuronal migration, but it is unknown how these signals are coordinated. In vitro studies suggested that the mastermind-like 1 (MAML1) gene, homologue of the Drosophila Mastermind, plays a role in coordinating the afore-mentioned signaling pathways, yet its role during cortical development remains largely unknown. Here we show that ectopic expression of dominant-negative MAML (dnMAML) causes exuberant neuronal production in the mouse cortex without disrupting neuronal migration. Comparing the transcriptional consequences of dnMAML and Neurog2 ectopic expression revealed a complex genetic network controlling the balance of progenitor expansion versus neuronal production. Manilpulation of MAML and Neurog2 in cultured human cerebral stem cells exposed interactions with the same set of signaling pathways. Thus, our data suggest that evolutionary changes that affect the timing, tempo and density of successive neuronal layers of the small lissencephalic rodent and large convoluted primate cerebral cortex depend on similar molecular mechanisms that act from the earliest developmental stages.

2019-09-09 | GSE76491 | GEO

Whole blood DNA methylation arrays of individuals with psoriatic arthritis, psoriasis vulgaris, and healthy control subjects

Project description:Genome-wide DNA methylation was analyzed to screen for differentially methylated CpG sites in the discovery phase to explore the role of DNA methylation CpG markers in the diagnosis of psoriatic arthritis patients.

2023-06-01 | GSE200376 | GEO

Genetics, sex and life experience influence DNA methylation in the mouse

Project description:Methylation of DNA is an essential epigenetic mark in mammals, intimately involved in gene regulation. The extent to which genetics, sex, and life experience influence genomic DNA methylation patterns are matters of intense current interest. We addressed this issue by intercrossing inbred mouse strains and analyzing DNA methylation at the base-pair level across the genome in somatic tissue from parents and from age-matched offspring of multiple families. In comparison across genotype, tens of thousands of differentially methylated CpG residues and thousands of differentially methylated regions were detected. Differential methylation at these loci was preserved on parental alleles in offspring, suggesting that CpG methylation is a very stable epigenetic mark largely preserved across generation, correlating with DNA sequence. In comparison of autosomal DNA methylation patterns across sex, thousands of differentially methylated CpG residues and hundreds of differentially methylated regions were detected, consistent with known biological parameters that differ between males and females. Finally, comparison of individual groups of animals within our study revealed a CpG methylation pattern that likely results from pregnancy and/or lactation that was restricted to female animals who had borne offspring, signifying that CpG methylation may provide a record of major life events. Collectively, our results demonstrate the stability of CpG methylation across generation, clarify the interplay of epigenetics with genetics and sex, and suggest that CpG methylation may serve as an epigenetic record of life events.

2018-10-24 | GSE106379 | GEO

Affinity purification of DNA binding proteins from HeLa extracts LC-MS/MS

Project description:The enhancer/promoter of the vitellogenin II (VTG) gene has been extensively studied as a model system of vertebrate transcriptional control. While deletion mutagenesis and in vivo footprinting identified the transcription factor (TF) binding sites governing its tissue specificity, DNase hypersensitivity- and DNA methylation studies revealed the epigenetic changes accompanying its hormone-dependent activation. Moreover, upon induction with estrogen (E2), the region flanking the estrogen-responsive element (ERE) was reported to undergo active DNA demethylation. We now show that although the VTG ERE is methylated in embryonic chicken liver and in LMH/2A hepatocytes, its induction by E2 was not accompanied by extensive demethylation. In contrast, E2 failed to activate a VTG enhancer/promoter-controlled luciferase reporter gene methylated by SssI. Surprisingly, this inducibility difference could be traced not to the ERE, but rather to a single CpG in an E-box (CACGTG) sequence upstream of the VTG TATA box, which is unmethylated in vivo, but methylated by SssI. We demonstrate that this E-box binds the upstream stimulating factor USF1/2. Selective methylation of the CpG within this binding site with an E-box-specific DNA methyltranferase Eco72IM was sufficient to attenuate USF1/2 binding in vitro and abolish the hormone-induced transcription of the VTG gene in the reporter system.

2020-05-27 | PXD015594 | Pride

Enhanced epigenetic profiling of classical human monocytes reveals a specific signature of healthy aging in the DNA methylome

Project description:The impact of healthy aging on molecular programming of immune cells is poorly understood. Here, we report comprehensive characterization of healthy aging in human classical monocytes, with a focus on epigenomic, transcriptomic, and proteomic alterations, as well as the corresponding proteomic and metabolomic data for plasma, using healthy cohorts of 20 young and 20 older males (~27 and ~64 years old on average). For each individual, we performed eRRBS-based DNA methylation profiling, which allowed us to identify a set of age-associated differentially methylated regions (DMRs) – a novel, cell-type specific signature of aging in DNA methylome. Hypermethylation events were associated with H3K27me3 in the CpG islands near promoters of lowly-expressed genes, while hypomethylated DMRs were enriched in H3K4me1 marked regions and associated with age-related increase of expression of the corresponding genes, providing a link between DNA methylation and age-associated transcriptional changes in primary human cells.

2022-02-16 | PXD021821 | Pride

Epigenetic reprogramming of immune cells in women with PCOS impact genes controlling reproductive function [RRBS]

Project description:Transcriptomic and genome-wide DNA methylation was performed on T helper cells using RNA-sequencing and Reduced Representation Bisulfite Sequencing, respectively. Specific genome-wide DNA methylation analysis of T helper cells from women with PCOS identified 5,581 differentially methylated CpG sites. Interestingly, functional gene ontology enrichment analysis showed that genes located at the proximity of differentially methylated CpG sites belong to pathways related to reproductive function and immune cell function. However, these genes were not altered at the transcriptomic level. Our results show that PCOS is associated with global and gene-specific DNA methylation remodelling in a cell-type specific manner.

2019-08-22 | GSE130581 | GEO

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