Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells

ABSTRACT: MicroRNAs (miRNAs) are crucial for normal embryonic stem (ES) cell self-renewal and cellular differentiation, but how miRNA gene expression is controlled by the key transcriptional regulators of ES cells has not been established. We describe here a new map of the transcriptional regulatory circuitry of ES cells that incorporates both protein-coding and miRNA genes, and which is based on high-resolution ChIP-seq data, systematic identification of miRNA promoters, and quantitative sequencing of short transcripts in multiple cell types. We find that the key ES cell transcription factors are associated with promoters for most miRNAs that are preferentially expressed in ES cells and with promoters for a set of silent miRNA genes. This silent set of miRNA genes is co-occupied by Polycomb Group proteins in ES cells and expressed in a tissue-specific fashion in differentiated cells. These data reveal how key ES cell transcription factors promote the miRNA expression program that contributes to self-renewal and cellular differentiation, and integrate miRNAs and their targets into an expanded model of the regulatory circuitry controlling ES cell identity. Keywords: ChIP-seq analysis of ES cell transcriptional regulators and chromatin modifications. Cell-type comparison of short RNA transcritome. Analysis of changes in short RNA transcritome upon Oct4 ablation.

ORGANISM(S): Mus musculus

PROVIDER: GSE11724 | GEO | 2008/07/30

SECONDARY ACCESSION(S): PRJNA106023

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Connecting microRNA genes to the core transcriptional regulatory circuitry of embryonic stem cells

Project description:MicroRNAs (miRNAs) are crucial for normal embryonic stem (ES) cell self-renewal and cellular differentiation, but how miRNA gene expression is controlled by the key transcriptional regulators of ES cells has not been established. We describe here a new map of the transcriptional regulatory circuitry of ES cells that incorporates both protein-coding and miRNA genes, and which is based on high-resolution ChIP-seq data, systematic identification of miRNA promoters, and quantitative sequencing of short transcripts in multiple cell types. We find that the key ES cell transcription factors are associated with promoters for most miRNAs that are preferentially expressed in ES cells and with promoters for a set of silent miRNA genes. This silent set of miRNA genes is co-occupied by Polycomb Group proteins in ES cells and expressed in a tissue-specific fashion in differentiated cells. These data reveal how key ES cell transcription factors promote the miRNA expression program that contributes to self-renewal and cellular differentiation, and integrate miRNAs and their targets into an expanded model of the regulatory circuitry controlling ES cell identity. Keywords: ChIP-seq analysis of ES cell transcriptional regulators and chromatin modifications. Cell-type comparison of short RNA transcritome. Analysis of changes in short RNA transcritome upon Oct4 ablation. ChIP-seq in murine embryonic stem cells for Oct4, Sox2 (2 runs), Nanog (2 runs), Tcf3 (2 runs), Suz12 (2 runs), H3K4me3 (4 runs), H3k79me2 (2 runs), H3k36me3 (2 runs) and whole cell extract input DNA (WCE, 2 runs). Short transcript sequencing from murine embryonic stem cells (mES, v6.5), mouse embryonic fibroblasts (MEF), murine neural precursor cells (NPC), and ZHBT-c4 cells (from Austin Smith) untreated (0h), with 12 hours of doxycyclin treatment (12h), and with 24 hours of doxycyclin treatment (24h).

2008-07-29 | E-GEOD-11724 | biostudies-arrayexpress

Chromatin immunoprecipitation of Oct4, Nanog and Suz12 in human and mouse embryonic stem cells to identify promoters for miRNAs

Project description:Understanding the transcriptional regulatory circuitry responsible for pluripotency and self-renewal in embryonic stem (ES) cells is fundamental to understanding human development and realizing the therapeutic potential of these cells. The transcription factor Oct4 and the chromatin-modifying Polycomb complex, key regulators of ES cell pluripotency and self-renewal, contribute to positive and negative control of a known set of protein-coding genes. MicroRNAs (miRNAs), non-coding transcripts that participate in post-transcriptional gene regulation are also important for normal pluripotency and self-renewal in ES cells, but there has been no systematic investigation of how miRNA expression is controlled by transcriptional regulators of ES cell identity. Here we identify promoters for miRNAs in the human and mouse genomes and describe the subset of these genes that are under the control of Oct4 and Polycomb in ES cells. We find that the majority of miRNAs that are uniquely or preferentially expressed in ES cells are bound by and dependent on Oct4. Oct4 also occupies a set of miRNA genes that are co-occupied by the Polycomb Group protein, Suz12. These miRNAs, repressed in ES cells, are later expressed in differentiated cells in a highly tissue-specific fashion, suggesting that they may contribute to cell-fate determinations. These data reveal how the core transcriptional regulatory circuitry of ES cells controls the miRNA expression program that contributes to pluripotency and self-renewal.

2010-12-01 | E-TABM-365 | biostudies-arrayexpress

Esrrb Regulates Specific Feed-Forward Loops to Transit from Pluripotency into Early Stages of Differentiation

Project description:Characterization of pluripotent states, in which cells can both self-renew or differentiate, with the irreversible loss of pluripotency, are important research areas in developmental biology. Although microRNAs (miRNAs) have been shown to be crucial for embryonic stem (ES) self-renewal maintenance and cellular differentiation, the role of miRNAs integrated into gene regulatory networks and its dynamic changes during these state transitions remain elusive. Here we describe the dynamic transcriptional regulatory circuitry of ES cells that incorporate protein-coding and miRNA genes based on microRNA array expression and quantitative sequencing of short transcripts upon the downregulation of the Estrogen Related Receptor Beta (Esrrb). The data reveals how Esrrb, a key stem cell transcription factor, regulates a specific ES cell miRNA expression program and integrates dynamic changes of feed forward loops contributing to the exit of the pluripotency state upon its downregulation. Together these findings provide new insights on the architecture of the combined transcriptional post-transcriptional regulatory network in stem cells.

2022-03-21 | GSE57371 | GEO

Esrrb Regulates Specific Feed-Forward Loops to Transit from Pluripotency into Early Stages of Differentiation (RNA-Seq)

2022-03-21 | GSE189678 | GEO

Chromatin immunoprecipitation of Tcf3, Oct4 and nanog in mouse embryonic stem cells

Project description:Embryonic stem cells have a unique regulatory circuitry, largely controlled by the transcription factors Oct4, Sox2 and Nanog, which generates a gene expression program necessary for pluripotency and self-renewal (Boyer et al. 2005; Loh et al. 2006; Chambers et al. 2003; Mitsui et al. 2003; Nichols et al. 1998). How external signals connect to this regulatory circuitry to influence embryonic stem cell fate is not known. We report here that a terminal component of the canonical Wnt pathway in embryonic stem cells, the transcription factor Tcf3, co-occupies promoters throughout the genome in association with the pluripotency regulators Oct4 and Nanog. Thus Tcf3 is an integral component of the core regulatory circuitry of ES cells, which includes an autoregulatory loop involving the pluripotency regulators. Both Tcf3 depletion and Wnt pathway activation cause increased expression of Oct4, Nanog and other pluripotency factors and enhance pluripotency and self-renewal. Our results reveal that the Wnt pathway, through Tcf3, brings developmental signals directly to the core regulatory circuitry of ES cells to influence the balance between pluripotency and differentiation.

2008-02-28 | E-TABM-409 | biostudies-arrayexpress

miR-126 Governs Human Leukemia Stem Cell Quiescence and Therapeutic Resistance

Project description:In acute myeloid leukemia (AML), leukemia stem cells (LSC) play a central role in disease progression and recurrence due to their intrinsic capacity for self-renewal and chemotherapy resistance. Whereas epigenetic mechanisms balance normal blood stem cell self-renewal and fate decisions, mutation and dysregulation of epigenetic regulators are considered fundamental to leukemia initiation and progression. Alterations in miRNA function represent a non-canonical epigenetic mechanism influencing malignant hematopoiesis, however the function of miRNA in human LSC remains undetermined. Here we show that miRNA profiling of fractionated AML populations defines an LSC-specific signature that is highly prognostic for patient survival. Gain- and loss-of-function analyses demonstrated that miR-126 restrained cell cycle progression, prevented differentiation, and increased self-renewal of human LSC. By targeting the G0 to G1 gatekeeper CDK3, miR-126 preserved LSC quiescence and promoted chemotherapy resistance. Thus, in AML, miRNAs influence patient outcome through post-transcriptional regulation of stemness programs in LSC.

2016-03-31 | PXD001994 | Pride

An integrated expression atlas of miRNAs and their promoters in human and mouse

Project description:MicroRNAs (miRNAs) are short non-coding RNAs with key roles in cellular regulation. We created the first integrated expression atlas of miRNAs and their promoters in mammalian cells by deep sequencing matched short RNA (sRNA) and Cap Analysis Gene Expression (CAGE) libraries from 492 RNA samples. Most samples were derived from human primary cells, allowing us to annotate each human miRNA by its sRNA expression profile across primary cell types. Promoters were identified for 1,357 human and 804 mouse miRNAs and showed strong sequence conservation between species, reflecting the importance of transcriptional regulation of miRNA expression. As primary and mature miRNA expression levels in the matched libraries were correlated, CAGE expression of primary miRNAs could be used as a proxy for the expression level of mature miRNAs, allowing us to extend the miRNA expression survey to the 1,829 human and 1,029 mouse CAGE libraries in FANTOM5. We thus provide the first broad atlas of miRNA expression in primary cells, as well as the largest map of miRNA promoters to date, establishing the foundation for detailed analysis of expression patterns and transcriptional control regions of miRNAs.

2017-08-16 | GSE98695 | GEO

Wdr5 mediates self-renewal and reprogramming via the embryonic stem cell core transcriptional network

Project description:The embryonic stem (ES) cell transcriptional and epigenetic networks are critical for the maintenance of ES cell self-renewal. However, it remains unclear whether components of these networks functionally interact and if so, what factors mediate such interactions. Here we show that WD-repeat protein-5 (Wdr5), a core member of the mammalian Trithorax (trxG) complex, positively correlates with the undifferentiated state and is a novel regulator of ES cell self-renewal. We demonstrate that Wdr5, an ‘effector’ of H3K4 methylation, interacts with the pluripotency transcription factor Oct4. In concordance, genome-wide ChIP-Seq and transcriptome analyses demonstrate overlapping gene regulatory functions between Oct4 and Wdr5. We show that the Oct4-Sox2-Nanog circuitry cooperates with trxG for transcriptional activation of key self-renewal regulators. Furthermore, Wdr5 expression is required for the efficient formation of induced pluripotent stem (iPS) cells. Collectively, these findings implicate an integrated model of transcriptional and epigenetic control, mediated by select trxG members, for the maintenance of ES cell self-renewal and somatic cell reprogramming. 7 Samples

2011-04-08 | E-GEOD-22934 | biostudies-arrayexpress

Comparison of Zfp706GT and ZfpGT REV ES cells in 2i

Project description:Self-renewal circuitry in embryonic stem (ES) cells is increasingly defined. How the robust pluripotency programme is dissolved to enable fate transition is less appreciated. We developed a forward genetic approach using haploid ES cells. We created libraries of transposon integrations and screened for persistent self-renewal in differentiation permissive culture. This yielded multiple mutants in the FGF/Erk and GSK3/Tcf3 modules known to drive differentiation, and in epigenetic modifiers implicated in lineage commitment. We also identified and validated factors not previously considered. These include the conserved small zinc finger protein Zfp706. Loss of Zfp706 function severely delays the exit from self-renewal. To asses a potential function of Zfp706 in regulation of gene expression we compared transcription profiles between Zfp706 gene trap mutant ES cells and genetic revertants. Assessment of differentially expressed genes in Zfp706 gene trap mutants obtained in a haploid ES cell screen for effectors of ES cell differentiation vs. genetic revertants generated by Flp-e mediated excision of the gene trap cassette

2014-02-05 | E-GEOD-53194 | biostudies-arrayexpress

β-catenin associated protein complex maintains ground state mouse embryonic stem cell by regulating lineage development

Project description:Mouse embryonic stem (ES) cells cultured in defined medium with MEK and GSK3 inhibitors (2i) resemble the pre-implantation epiblast in the ground state, with full development capacity including the somatic lineages and the germline. Although β-catenin is known to be crucial for naive pluripotency of ES cells, the mechanism is not fully understood. Here we showed that β-catenin interacted with a repressive protein complex to maintain the ground state of ES cells by fine-tuning their lineage development potential. Absence of β-catenin impaired ES cell self-renewal without affecting the core self-renewal circuitry of Oct4, Sox2 and Nanog as well as other pluripotency factors. However, β-catenin-deficient cells showed a primed state transcriptional signature with perturbed expression of germline and neuronal lineage genes. Knockdown of Tcf7l1, the repressor in canonical Wnt signaling pathway, did not completely rescue the β-catenin-deficient phenotype of ES cells. Mechanistically, β-catenin formed a novel biochemical complex with E2F6, HP1γ and HMGA2 to restrain ES cells from differentiation by co-occupying the promoters of germline and neuronal lineage regulators independent of TCF7L1. Overall, out work showed that β-catenin maintained ground state ES cells by orchestrating their development plasticity through a repressive protein complex with E2F6, HP1γ and HMGA2.

2020-08-20 | GSE108620 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

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