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Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE41316 | GEO | 2013/02/20

SECONDARY ACCESSION(S): PRJNA176497

REPOSITORIES: GEO

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Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes.

Project description:Polycomb group (PcG) proteins play important roles in repressing lineage-specific genes and maintaining the undifferentiated state of mouse embryonic stem cells (mESCs). However, how PcG proteins are recruited to their target genes is largely unknown. Here, we show that the H3K36-specific histone demethylase Kdm2b is highly expressed in mESCs and regulated by the pluripotent factors Oct4 and Sox2 directly. Depletion of Kdm2b in mESCs causes de-repression of lineage-specific genes and induces early differentiation. The function of Kdm2b depends on its CxxC-ZF domain, which mediates its genome-wide binding to CpG islands (CGIs). Kdm2b interacts with the core components of polycomb repressive complex 1 (PRC1) and recruits the complex to the CGIs of early lineage-specific genes. Thus, our study not only reveals an Oct4-Sox2-Kdm2b-PRC1-CGI regulatory axis and its function in maintaining the undifferentiated state of mESCs, but also demonstrates a critical function of Kdm2b in recruiting PRC1 to the CGIs of lineage-specific genes to repress their expression.

| S-EPMC4078788 | biostudies-literature

Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes

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

2013-02-20 | E-GEOD-41316 | biostudies-arrayexpress

Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of lineage genes [Expression profiling]

Project description:Polycomb group (PcG) proteins play important roles in repressing lineage-specific genes and maintaining the undifferentiated state of mouse embryonic stem cells (mESCs). However, the mechanisms by which PcG proteins are recruited to their targets are largely unknown. Here, we show that the histone demethylase Kdm2b is highly expressed in mESCs and regulated by the pluripotent factors Oct4/Sox2 directly. Depletion of Kdm2b in mESCs causes de-repression of lineage-specific genes and induces early differentiation. The function of Kdm2b depends on its CXXC-ZF domain, which mediates Kdm2b’s genome-wide binding to CpG islands (CGIs). Kdm2b interacts with the core components of the Polycomb repressive complex 1 (PRC1) and recruits the complex to the CGIs of early lineage-specific genes. Thus, our study not only reveals a novel Oct4/Sox2-Kdm2b-PRC1-CGI regulatory axis and its function in maintaining undifferentiated state of mESCs, but also demonstrates a critical function of Kdm2b in recruiting PRC1 to the CGIs of lineage-specific genes to repress their expression. In this dataset, we include the expression data for control and Kdm2b knockdown mouse embryonic stem cells. We analyzed the gene expression in control and Kdm2b knockdown mouse embryonic stem cells using the Affymetrix MoGene-1_0-st-v1 platform.

2013-02-20 | E-GEOD-41298 | biostudies-arrayexpress

Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of lineage genes [ChIP-Seq]

Project description:Polycomb group (PcG) proteins play important roles in repressing lineage-specific genes and maintaining the undifferentiated state of mouse embryonic stem cells (mESCs). However, the mechanisms by which PcG proteins are recruited to their targets are largely unknown. Here, we show that the histone demethylase Kdm2b is highly expressed in mESCs and regulated by the pluripotent factors Oct4/Sox2 directly. Depletion of Kdm2b in mESCs causes de-repression of lineage-specific genes and induces early differentiation. The function of Kdm2b depends on its CXXC-ZF domain, which mediates Kdm2b’s genome-wide binding to CpG islands (CGIs). Kdm2b interacts with the core components of the Polycomb repressive complex 1 (PRC1) and recruits the complex to the CGIs of early lineage-specific genes. Thus, our study not only reveals a novel Oct4/Sox2-Kdm2b-PRC1-CGI regulatory axis and its function in maintaining undifferentiated state of mESCs, but also demonstrates a critical function of Kdm2b in recruiting PRC1 to the CGIs of lineage-specific genes to repress their expression. In this dataset, we include the ChIP-seq data of Kdm2b, Ezh2 and Ring1b in both control and Kdm2b knock down mouse embryonbic stem cells.

2013-02-20 | E-GEOD-41314 | biostudies-arrayexpress

Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of lineage genes [ChIP-Seq]

Project description:Polycomb group (PcG) proteins play important roles in repressing lineage-specific genes and maintaining the undifferentiated state of mouse embryonic stem cells (mESCs). However, the mechanisms by which PcG proteins are recruited to their targets are largely unknown. Here, we show that the histone demethylase Kdm2b is highly expressed in mESCs and regulated by the pluripotent factors Oct4/Sox2 directly. Depletion of Kdm2b in mESCs causes de-repression of lineage-specific genes and induces early differentiation. The function of Kdm2b depends on its CXXC-ZF domain, which mediates Kdm2b’s genome-wide binding to CpG islands (CGIs). Kdm2b interacts with the core components of the Polycomb repressive complex 1 (PRC1) and recruits the complex to the CGIs of early lineage-specific genes. Thus, our study not only reveals a novel Oct4/Sox2-Kdm2b-PRC1-CGI regulatory axis and its function in maintaining undifferentiated state of mESCs, but also demonstrates a critical function of Kdm2b in recruiting PRC1 to the CGIs of lineage-specific genes to repress their expression.

2013-02-20 | GSE41314 | GEO

Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of lineage genes [Expression profiling]

Project description:Polycomb group (PcG) proteins play important roles in repressing lineage-specific genes and maintaining the undifferentiated state of mouse embryonic stem cells (mESCs). However, the mechanisms by which PcG proteins are recruited to their targets are largely unknown. Here, we show that the histone demethylase Kdm2b is highly expressed in mESCs and regulated by the pluripotent factors Oct4/Sox2 directly. Depletion of Kdm2b in mESCs causes de-repression of lineage-specific genes and induces early differentiation. The function of Kdm2b depends on its CXXC-ZF domain, which mediates Kdm2b’s genome-wide binding to CpG islands (CGIs). Kdm2b interacts with the core components of the Polycomb repressive complex 1 (PRC1) and recruits the complex to the CGIs of early lineage-specific genes. Thus, our study not only reveals a novel Oct4/Sox2-Kdm2b-PRC1-CGI regulatory axis and its function in maintaining undifferentiated state of mESCs, but also demonstrates a critical function of Kdm2b in recruiting PRC1 to the CGIs of lineage-specific genes to repress their expression. In this dataset, we include the expression data for control and Kdm2b knockdown mouse embryonic stem cells.

2013-02-20 | GSE41298 | GEO

Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes

Project description:Kdm2b maintains murine embryonic stem cell status by recruiting PRC1 complex to CpG islands of developmental genes

| PRJNA176497 | ENA

KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands.

Project description:CpG islands (CGIs) are associated with most mammalian gene promoters. A subset of CGIs act as polycomb response elements (PREs) and are recognized by the polycomb silencing systems to regulate expression of genes involved in early development. How CGIs function mechanistically as nucleation sites for polycomb repressive complexes remains unknown. Here we discover that KDM2B (FBXL10) specifically recognizes non-methylated DNA in CGIs and recruits the polycomb repressive complex 1 (PRC1). This contributes to histone H2A lysine 119 ubiquitylation (H2AK119ub1) and gene repression. Unexpectedly, we also find that CGIs are occupied by low levels of PRC1 throughout the genome, suggesting that the KDM2B-PRC1 complex may sample CGI-associated genes for susceptibility to polycomb-mediated silencing. These observations demonstrate an unexpected and direct link between recognition of CGIs by KDM2B and targeting of the polycomb repressive system. This provides the basis for a new model describing the functionality of CGIs as mammalian PREs.DOI:http://dx.doi.org/10.7554/eLife.00205.001.

| S-EPMC3524939 | biostudies-literature

KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands

Project description:This SuperSeries is composed of the SubSeries listed below.

2012-12-26 | GSE41267 | GEO

KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands

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

2012-12-26 | E-GEOD-41267 | biostudies-arrayexpress