Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Glis1 Activate Glycolytic Process and Increase H3K27Ac Level on Pluripotent and Second Wave Genes Promoter Facilitating Pluripotency Induction [RNA-Seq]

ABSTRACT: Metabolic activity possess a crucial role during cell fate determination. Here, we show that maternal transcriptional factor Glis1 could not only promote normal MEF reprogramming but also enable aging MEF reprogramming. By association ChIP-seq and RNA-seq, we found that Glis1 could bind and activate glycolytic genes, and bind and suppress somatic state genes simultaneously during reprogramming. While knockdown phosphoglyceric kinase (Pgk1) impeded reprogramming efficiency which indicates that Glis1-glycolytic process axes is required for Glis1 function. Metabolic analysis indicated that the level of acetyl-CoA has a significant fluctuation upon Glis1 induction or silence. Acetate, a precursor of acetyl-CoA rescued the effects on reprogramming in a time-dependent manner when knockdown endogenous Glis1. The fluctuation of Ac-CoA changed the level of H3K27Ac, especially in pluripotent genes and “second wave” genes promoter, and activated the expression of endogenous pluripotency genes in advance subsequently. In conclusion, we demonstrate the exactly novel mechanism of Glis1 in pluripotency acquisition.

ORGANISM(S): Mus musculus

PROVIDER: GSE131491 | GEO | 2020/06/24

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Glis1 Activate Glycolytic Process and Increase H3K27Ac Level on Pluripotent and Second Wave Genes Promoter Facilitating Pluripotency Induction [ChIP-Seq]

Project description:Metabolic activity possess a crucial role during cell fate determination. Here, we show that maternal transcriptional factor Glis1 could not only promote normal MEF reprogramming but also enable aging MEF reprogramming. By association ChIP-seq and RNA-seq, we found that Glis1 could bind and activate glycolytic genes, and bind and suppress somatic state genes simultaneously during reprogramming. While knockdown phosphoglyceric kinase (Pgk1) impeded reprogramming efficiency which indicates that Glis1-glycolytic process axes is required for Glis1 function. Metabolic analysis indicated that the level of acetyl-CoA has a significant fluctuation upon Glis1 induction or silence. Acetate, a precursor of acetyl-CoA rescued the effects on reprogramming in a time-dependent manner when knockdown endogenous Glis1. The fluctuation of Ac-CoA changed the level of H3K27Ac, especially in pluripotent genes and “second wave” genes promoter, and activated the expression of endogenous pluripotency genes in advance subsequently. In conclusion, we demonstrate the exactly novel mechanism of Glis1 in pluripotency acquisition.

2020-06-24 | GSE131426 | GEO

RNA-sequencing analysis of glucose and acetate regulated transcripts in glioblastoma cells

Project description:Our studies indicate that glucose and acetate can regulate histone acetylation by altering the acetyl-CoA concentrations in the cell. The purpose of this study was to to determine whether specific gene sets correlated with acetyl-CoA availability. We conclude that 10% of glucose-regulated genes are acetyl-CoA regulated genes (genes suppressed or induced by low glucose and reversed by acetate). Acetate usually regulated gene expression in the same direction as glucose, suggesting that acetyl-CoA is a key mediator of glucose-dependent gene expression. The experiments were performed in quadruplicates for each condition with a total of 12 samples

2014-08-05 | E-GEOD-57488 | biostudies-arrayexpress

Metabolic control of primed human pluripotent stem cell fate and function by the miR-200c-SIRT2 axis

Project description:A hallmark of cancer cells is the metabolic switch from oxidative phosphorylation (OXPHOS) to glycolysis, a phenomenon referred to as the “Warburg effect”, which is also observed in primed human pluripotent stem cells (hPSCs). Here, we report that downregulation of SIRT2 and upregulation of SIRT1 is a molecular signature of primed hPSCs and that SIRT2 critically regulates metabolic reprogramming during induced pluripotency by targeting glycolytic enzymes including aldolase, glyceraldehyde-3-phosphate dehydrogenase, phosphoglycerate kinase, and enolase. Remarkably, knockdown of SIRT2 in human fibroblasts resulted in significantly decreased OXPHOS and increased glycolysis. In addition, we found that miR-200c-5p specifically targets SIRT2, downregulating its expression. Furthermore, SIRT2 overexpression in hPSCs significantly affected energy metabolism, altering stem cell functions such as pluripotent differentiation properties. Taken together, our results identify the miR-200c-SIRT2 axis as a key regulator of metabolic reprogramming (Warburg-like effect), via regulation of glycolytic enzymes, during human induced pluripotency and pluripotent stem cell function. To address our hypothesis that acetylation affects the metabolic switch, we compared protein acetylation in hESCs and hDFs by liquid chromatography-tandem mass spectrometry (LCMS/ MS) analyses following immunoprecipitation with acetyl-Lys antibody.

2018-10-26 | PXD006036 | Pride

RNA-sequencing analysis of glucose and acetate regulated transcripts in glioblastoma cells

2014-08-05 | GSE57488 | GEO

Nucleoside-Diphosphate Kinase 1 and 2 are master regulators of a liver protective response to high fat diet [ChIP-seq]

Project description:Fatty acid homeostasis is critical for normal cellular physiology and leads to severe diseases when deregulated. Here we report Nucleoside-Diphosphate Kinase 1 and 2 (NME1/2) as major cellular co-enzyme A (CoA) and acetyl-CoA binding proteins and negative regulators of de novo lipogenesis (DNL). Structural studies demonstrate that Nme1 recognizes CoA through its nucleotide moiety, which competes for binding with ADP/ATP. By using a Nme2 ko mouse model, we observe that NME2 is required for the gene transcriptional response to a high fat diet (HFD) in liver cells, leading to a repression of lipogenesis and the activation of a protective gene response. Nme2 ko mice submitted to a HFD challenge are unable to repress key lipogenic genes, resulting in an excessive triglyceride synthesis and liver steatosis. Mechanistically, the NME2-dependent down-regulation of DNL in response to HFD changes the balance for the use of acetyl-CoA between the competing paths of acetylation and DNL, thereby increasing TSS-targeted histone acetylation and gene activation. A structure-guided generation of a NME1 mutant, with intact NDK activity, but unable to bind CoA, directly demonstrates the functional impact of acetyl-CoA/CoA binding by NME1/2 in repressing DNL. Taken together, these findings highlight a yet unknow protective liver response to HFD, regulated by multi-ligand binding proteins which act as direct sensors for the cellular levels of NDP/NTP and CoA/acetyl-CoA.

2023-08-01 | GSE198687 | GEO

Nucleoside-Diphosphate Kinase 1 and 2 are master regulators of a liver protective response to high fat diet [RNA-seq]

2023-08-01 | GSE198686 | GEO

Accessing Pluripotency from the Somatic Side

Project description:We report that Jdp2, Jhdm1b, Mkk6, Glis1, Nanog, Essrb and Sall4 (7F) convert MEFs to chimera competent iPSCs with fast kinetics. Time lapse microscopy reveal morphological changes distinct for 7F and Yamanaka factor (YF) reprogramming. Bulk transcriptomic analyses suggest that 7F and YF share 927 up and 548 down regulated genes, but differ in 1138 YF and 427 7F specifically activated genes. Single cell RNA sequencing reveals a fate path that can be further resolved into a cell fate continuum based on a MEF/ESC scoring system. A crossing point marks the transition in the continuum from somatic to pluripotent fates. By sampling the leading cells along this continuum, we identified transition stages marked by novel nu-clear factors and cell surface molecules. Our results reveal an efficient path to pluripotency and suggest that cell fate is governed by intrinsic fac-tors accessible by diverse approaches

2020-01-01 | GSE110208 | GEO

A metabolism-epigenome axis controls early events in CD4+ T cell activation

Project description:Upon antigen-specific T Cell Receptor (TCR) engagement, human CD4+ T cells proliferate and differentiate, a process associated with rapid transcriptional changes and metabolic reprogramming utilizing aerobic glycolysis together with maintenance of oxidative phosphorylation1,2. However, the role of glycolytic-reprogramming during T-cell activation remains largely unclear3,4,5. Here, we show that maintenance of cytosolic pyruvate production is an essential requirement for remodeling of the CD4+ T cell epigenome after TCR-engagement. Furthermore, we provide evidence that the local inflammatory environment sustains metabolic reprogramming of CD4+ T-cells and impacts histone modification in a pyruvate-dependent manner. Mechanistically, we demonstrate that rapid and sustained generation of cytosolic, but not mitochondrial, pyruvate is an essential step for acetyl-coA production and subsequent H3K27ac epigenome remodeling. TCR-activation was found to induce nuclear import of pyruvate dehydrogenase (PDH) and its association with both the p300 acetyltransferase and histone H3K27ac. Disrupting PDH nuclear import impacted expression of activation-induced genes. These results reveal a direct connection between CD4+ T cell metabolic reprogramming and transcriptional regulation, with the generation of cytosolic pyruvate being an essential step in T cell activation. These data support tight integration of metabolic enzymes and histone modifying enzymes, allowing metabolic reprogramming to fuel CD4+ T cell activation.

2023-10-27 | PXD018132 | Pride

Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts by Jdp2, Glis1, Essrb and Sall4 [ATAC-seq]

Project description:Reprogramming somatic cells to pluripotency represents a paradigm for cell fate determination. A binary logic of closing and opening chromatin provides a simple way to understand iPSC reprogramming driven by both Yamanaka factors or chemicals. Here we apply this logic to the design a four factor combination, Jdp2, Glis1, Essrb and Sall4 (4F), that reprogram MEFs to chimera competent iPSCs efficiently. RNA- and ATAC-seq reveal differences between JGES and 7F induced pluripotency, 7IP and JGES IP, in transcriptomic and chromatin accessibility dynamics(CAD). Sall4 emerges as a dominant force that can close and open chromatin with the help of Jdp2 and Glis1 in resetting somatic chromatin to a pluripotent state. These results reveal a previously unknown path between somatic and pluripotent states, open a door for cell fate control.

2022-11-05 | GSE140007 | GEO

Induction of Pluripotent Stem Cells from Mouse Embryonic Fibroblasts by Jdp2, Glis1, Essrb and Sall4 [RNA-seq]

2022-11-05 | GSE140006 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data