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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. 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Milica Putnik

PROVIDER: E-GEOD-62177 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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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

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

2014-10-08 | GSE62177 | GEO

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

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

Acute depletion redefines the division of labor among DNA methyltransferases in methylating the human genome [MBD-seq]

Project description:Global patterns of DNA methylation, mediated by the DNA methyltransferases (DNMTs), are disrupted in all cancers by mechanisms that remain largely unknown, hampering their development as therapeutic targets. Combinatorial acute depltion of all DNMTs in a pluripotent human tumor cell line, followed by epigenome and transcriptome analysis, revealed DNMT functions in unprecedented detail. DNMT3B occupancy regulates methylation during differentiation, while an unexpected interplay was discovered in which DNMT1 and DNMT3B antithetically regulate methylation and hydroxymethylation in gene bodies, a finding confirmed in other cell types. DNMT3B mediated nonCpG methylation, while DNMT3L influenced the activity of DNMT3B toward nonCpG versus CpG site methylation. Taken together, these data reveal new functional targets of each DNMT suggesting that isoform selective inhibition would be therapeutically advantageous. NCCIT cells were transfected with siRNAs against DNMT3B and a no-target control. Genomic DNA was extracted, and subsequently applied to affinity MBD-bound magnetic beads (Ribomed) to enrich methylated DNA sequences.

2014-10-20 | E-GEOD-54842 | biostudies-arrayexpress

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

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-10-08 | E-GEOD-62178 | biostudies-arrayexpress

Correlation between gene expression responses to FUS, EWS, and TAF15 reduction and the stress granule sequestering capacity

Project description:Analysis of differentially expressed genes after siRNA mediated knock-down of the FET-family of proteins; the FUS, EWS, and TAF15 proteins. The FET-proteins are thought to function as transcription factors, and this hypothesis is tested in the present study. Results provide important information of the genes which expression are controlled by the FET-family of proteins. Total RNA obtained HEK293-cells transfected with siRNA targeted against the FUS, EWS, or TAF15 mRNA, or a combination of all three of them. Control cells are transfected with an equal amount of unspecific siRNA without known targets.

2012-02-07 | E-GEOD-35578 | biostudies-arrayexpress

The Senescent Methylome and its relationship with cancer, ageing, and germline genetic variation in humans (methylation experiment 2)

Project description:Cellular senescence is a stable arrest of proliferation and is considered a key component of processes associated with carcinogenesis and other ageing-related phenotypes. However, till now, biological markers that define senescence on a genome-wide scale have been limited. Here, we report a DNA methylomic analysis of actively dividing and deeply senescent normal human epithelial cells, identifying 3,852 senescence-associated differentially methylated positions (senDMPs). We find that this human senDMP signature is positively and significantly correlated with both cancer and ageing-associated methylomic dynamics. We also identify germline genetic variants, including those associated with the p16INK4A locus, that are associated with the presence of in vivo senDMP signatures. Importantly, we also demonstrate that the senDMP signature can be effectively reversed in a newly-developed protocol of transient cellular rejuvenation. The senDMP signature has significant potential for understanding some of the key (epi)genetic etiological factors that lead to cancer and age-related diseases in humans. Bisulphite converted DNA from the HMECs at early passage (EP), deep senescence (DS), deep senescence + p16 siRNA (DS+p16siRNA) at two different time points and FACS for cell cycle at EP were hybridised to the Illumina Infinium 450k Human Methylation Beadchip

2015-07-26 | E-GEOD-69046 | biostudies-arrayexpress

The Senescent Methylome and its relationship with cancer, ageing, and germline genetic variation in humans (methylation experiment 1)

2015-07-26 | E-GEOD-56719 | biostudies-arrayexpress

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

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