Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

An essential role for UTX in resolution and activation of bivalent promoters

ABSTRACT: In the present study, we show that UTX plays an essential role in resolving and activating many retinoic acid (RA)-inducible bivalent genes during the RA-driven differentiation of mouse ESCs treated with a physiologically relevant RA concentration (0.2 μM). We showed that UTX loss and UTX knockdown interfered with the RA-induced differentiation of mouse ESCs. Therefore, our findings indicate that the UTX-mediated resolution and activation of many RA-inducible bivalent genes, including numerous Hoxa-d cluster genes, are required for RA-driven differentiation of mouse ESCs.

ORGANISM(S): Mus musculus

PROVIDER: GSE76692 | GEO | 2016/02/05

SECONDARY ACCESSION(S): PRJNA308325

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

An essential role for UTX in resolution and activation of bivalent promoters

Project description:In the present study, we show that UTX plays an essential role in resolving and activating many retinoic acid (RA)-inducible bivalent genes during the RA-driven differentiation of mouse ESCs treated with a physiologically relevant RA concentration (0.2 Î¼M). We showed that UTX loss and UTX knockdown interfered with the RA-induced differentiation of mouse ESCs. Therefore, our findings indicate that the UTX-mediated resolution and activation of many RA-inducible bivalent genes, including numerous Hoxa-d cluster genes, are required for RA-driven differentiation of mouse ESCs. ChIP-Seq data for H3K4me3 and H3K27me3 were generated along with input data for mouse stem cells with wild type or UTX-depleted genotype and with or without RA treatment.

2016-02-05 | E-GEOD-76692 | biostudies-arrayexpress

Mammalian CDC14 control differentiation from pluripotent cells by modulating UTF1 activity on bivalent promoters

Project description:CDC14 phosphatases are critical components of the cell cycle machinery that drives exit from mitosis in yeast. However, the two mammalian paralogs, CDC14A and CDC14B, are dispensable for cell cycle progression or exit, and their function remains unclear. By generating a double Cdc14a; Cdc14b-null mouse model, we report here that CDC14 phosphatases control cell differentiation in pluripotent cells and their absence results in deficient development of the neural system. Lack of CDC14 impairs neural differentiation from embryonic stem cells (ESCs) accompanied by deficient induction of genes controlled by bivalent promoters. During ESC differentiation, CDC14 directly dephosphorylates and destabilizes Undifferentiated embryonic Transcription Factor 1 (UTF1), a critical regulator of stemness. In the absence of CDC14, increased UTF1 levels prevent the firing of bivalent promoters, resulting in defective induction of the transcriptional programs required for differentiation. These results suggest that mammalian CDC14 phosphatases function during the terminal exit from the cell cycle by modulating the transition from the pluripotent to the differentiated chromatin state, at least partially by controlling chromatin dynamics and transcription in a UTF1-dependent manner.

2022-10-31 | PXD030296 | Pride

Mammalian Dpy-30 regulates genomic H3K4 methylation and is essential for ES cell fate specification

Project description:H3K4 methylation is associated with active genes and, along with H3K27 methylation, is part of a bivalent chromatin mark that typifies poised developmental genes in ESCs. However, its functional roles in ESC maintenance and differentiation are not established. Here we show that mammalian Dpy-30, a core subunit of SET1/MLL complexes, biochemically modulates H3K4 methylation in vitro, and directly regulates chromosomal H3K4me3 throughout the mammalian genome. Depletion of Dpy-30 does not affect ESC self-renewal, but significantly alters the differentiation potential of ESCs, particularly along the neural lineage. The differentiation defect is accompanied by defects in gene induction and H3K4 methylation at key developmental loci. Our results provide strong experimental evidence for the hypothesis that H3K4 methylation is an essential functional component of the bivalent mark during activation of developmental genes in ESCs. Total RNAs from control or knockdown cells before and after RA-mediated differentiation were subjected to Illumina microarray analyses. ChIP-enriched DNA from mouse ES cells was analyzed by Solexa sequencing.

2011-02-01 | E-GEOD-26136 | biostudies-arrayexpress

Mll2 branch of the COMPASS family regulates bivalent promoters in mouse embryonic stem cells

Project description:Promoters of many developmentally regulated genes, in the embryonic stem cell state, have a bivalent mark of H3K27me3 and H3K4me3, proposed to confer precise temporal activation upon differentiation. Although Polycomb repressive complex 2 is known to implement H3K27 trimethylation, the COMPASS family member responsible for H3K4me3 at bivalently marked promoters was previously unknown. Here, we identify Mll2 (KMT2b) as the enzyme catalyzing H3K4 trimethylation at bivalently marked promoters in embryonic stem cells. Although H3K4me3 at bivalent genes is proposed to prime future activation, we detected no substantial defect in rapid transcriptional induction after retinoic acid treatment in Mll2-depleted cells. Our identification of the Mll2 complex as the COMPASS family member responsible for H3K4me3 marking at bivalent promoters provides an opportunity to reevaluate and experimentally test models for the function of bivalency in the embryonic stem cell state and in differentiation. ChIP-Seq in mouse embryonic stem (mES) cells for MLL2. ChIP-seq of H3K4me1, H3K4me3 and H3K27me3 for mES cells with RNAi against MLL2(shMLL2) and control (shGFP). ChIP-seq of H3K4me3 in mES cells with RNAi against MLL3 (shMLL3). RNA-seq of mES cells with RNAi against MLL2 and control (shGFP). RNA-seq of control mES cells (shGFP) or MLL2 RNAi mES cells (shMLL2) induced with RA for 6h and 12h.

2013-08-11 | E-GEOD-48172 | biostudies-arrayexpress

UTX Regulates Human Neural Differentiation and Dendritic Morphology by Resolving Bivalent Promoters

Project description:UTX Regulates Human Neural Differentiation and Dendritic Morphology by Resolving Bivalent Promoters

| PRJNA639440 | ENA

TET1 interactome by SILAC IP-MS in mouse ESCs

Project description:TET1 maintains hypomethylation at bivalent promoters through its catalytic activity in embryonic stem cells (ESCs). However, whether and how TET1 exerts catalytic activity-independent functions in regulating bivalent genes is not well understood. Therefore, we mapped the TET1 interactome in mouse ESCs using a SILAC IP-MS proteomics approach.

2022-06-10 | PXD033587 | Pride

Mammalian CDC14 phosphatases control bivalent promoters and exit from stemness in pluripotent cells [snGEX]

Project description:CDC14 phosphatases are critical components of the cell cycle machinery that drives exit from mitosis in yeast. However, the two mammalian paralogs, CDC14A and CDC14B, are dispensable for cell cycle progression or exit, and their function remains unclear. By generating a double Cdc14a; Cdc14b -null mouse model, we report here that CDC14 phosphatases control cell differentiation in pluripotent cells, and their absence results in deficient development of the neural system. Lack of CDC14 impairs neural differentiation from embryonic stem cells (ESCs) accompanied by deficient induction of genes controlled by bivalent promoters. CDC14 directly dephosphorylates and destabilizes Undifferentiated embryonic Transcription Factor 1 (UTF1) during the exit from stemness. Multiomic single-cell analysis of differentiating ESCs suggest that increased UTF1 levels in the absence of CDC14 prevent the firing of bivalent promoters required for differentiation. These results, along recent data suggesting a critical role for cell cycle kinases in pluripotency, suggest that cell cycle kinase-phosphatase modules such as CDK-CDC14 are critical for linking cell cycle regulation and self-renewal, with a specific function for CDC14 phosphatases modulating key epigenetic regulators during the terminal exit from pluripotency.

2022-10-31 | GSE196139 | GEO

Mammalian CDC14 phosphatases control bivalent promoters and exit from stemness in pluripotent cells [snATAC-Seq]

Project description:CDC14 phosphatases are critical components of the cell cycle machinery that drives exit from mitosis in yeast. However, the two mammalian paralogs, CDC14A and CDC14B, are dispensable for cell cycle progression or exit, and their function remains unclear. By generating a double Cdc14a; Cdc14b -null mouse model, we report here that CDC14 phosphatases control cell differentiation in pluripotent cells, and their absence results in deficient development of the neural system. Lack of CDC14 impairs neural differentiation from embryonic stem cells (ESCs) accompanied by deficient induction of genes controlled by bivalent promoters. CDC14 directly dephosphorylates and destabilizes Undifferentiated embryonic Transcription Factor 1 (UTF1) during the exit from stemness. Multiomic single-cell analysis of differentiating ESCs suggest that increased UTF1 levels in the absence of CDC14 prevent the firing of bivalent promoters required for differentiation. These results, along recent data suggesting a critical role for cell cycle kinases in pluripotency, suggest that cell cycle kinase-phosphatase modules such as CDK-CDC14 are critical for linking cell cycle regulation and self-renewal, with a specific function for CDC14 phosphatases modulating key epigenetic regulators during the terminal exit from pluripotency.

2022-10-31 | GSE196137 | GEO

Mammalian CDC14 control differentiation from pluripotent cells by modulating UTF1 activity on bivalent promoters

2022-10-31 | GSE191197 | GEO

Asf1a resolves bivalent chromatin domains for the induction of lineage-specific genes during mouse embryonic stem cell differentiation

Project description:Bivalent chromatin domains containing both repressive H3K27me3 and active H3K4me3 modifications are barriers for the expression of lineage-specific genes in embryonic stem (ES) cells and must be resolved for the transcription induction of these genes during differentiation, a process that remains largely unknown. Here, we show that Asf1a, a histone chaperone involved in both nucleosome assembly and disassembly, regulates the resolution of bivalent domains and activation of lineage-specific genes during mouse ES cell differentiation. Deletion of Asf1a does not affect the silencing of pluripotent genes, but compromises the expression of lineage-specific genes during ES cell differentiation. Mechanistically, the Asf1a-histone interaction, but not the role of Asf1a in nucleosome assembly is required for gene transcription. Asf1a is recruited to several bivalent promoters, partially through association with transcription factors, and mediates nucleosome disassembly during differentiation. We suggest that Asf1a-mediated nucleosome disassembly provides a means for resolution of bivalent domain barriers for induction of lineage-specific genes during differentiation.

2018-06-22 | GSE114424 | 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