Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA369130 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR5210260_1.fastq.gz | Fastqsanger.gz | |||
| SRR5210260_2.fastq.gz | Fastqsanger.gz | |||
| SRR5210261_1.fastq.gz | Fastqsanger.gz | |||
| SRR5210261_2.fastq.gz | Fastqsanger.gz | |||
| SRR5210252_1.fastq.gz | Fastqsanger.gz |
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Project description:Polycomb repressive complex 1 (PRC1) plays essential roles in cell fate determination. Recent studies have found that the composition of mammalian PRC1 is particularly varied and complicated, whereas the function of such variant PRC1 complexes on cell fate determination remains unknown. Here we show that Kdm2b, which recruits a variant PRC1 complex (PRC1.1) to CpG islands (CGIs), elevates Oct4 induced somatic reprogramming. Interaction with PRC1 is critical for Kdm2b’s promotion on the process of induced pluripotency. Furthermore, we find that bone morphogenetic proteins (BMPs) repress Oct4/Kdm2b induced somatic reprogramming selectively. Mechanistically, BMP-Smad pathway attenuates PRC1.1 occupation and H2AK119 ubiquitination on development genes, resulting in the release of meso-endoderm factors such as Sox17 and suppression of somatic reprogramming. These observations reveal that PRC1.1 participates in the establishment of pluripotency as well as cellular differentiation and identify BMP signal as a modulator of PRC1.1 function.
2017-11-19 | GSE93974 | GEO
Project description:Polycomb repressive complex 1 (PRC1) plays essential roles in cell fate determination. Recent studies have found that the composition of mammalian PRC1 is particularly varied and complicated, whereas the function of such variant PRC1 complexes on cell fate determination remains unknown. Here we show that Kdm2b, which recruits a variant PRC1 complex (PRC1.1) to CpG islands (CGIs), elevates Oct4 induced somatic reprogramming. Interaction with PRC1 is critical for Kdm2b’s promotion on the process of induced pluripotency. Furthermore, we find that bone morphogenetic proteins (BMPs) repress Oct4/Kdm2b induced somatic reprogramming selectively. Mechanistically, BMP-Smad pathway attenuates PRC1.1 occupation and H2AK119 ubiquitination on development genes, resulting in the release of meso-endoderm factors such as Sox17 and suppression of somatic reprogramming. These observations reveal that PRC1.1 participates in the establishment of pluripotency as well as cellular differentiation and identify BMP signal as a modulator of PRC1.1 function.
2017-11-19 | GSE93972 | GEO
Project description:The histone lysine demethylase protein, KDM2B, associates with the PCGF1/PRC1 complex and binds to non-methylated DNA through its ZF-CxxC domain, providing a possible molecular link between CpG island elements and polycomb nucleation (Farcas et al., 2012, Wu et al., 2013). Here, a novel genetic system was designed in which PCGF1/PRC1 targeting could be disrupted in vivo through the ablation of KDM2B-mediated DNA binding. To ablate PCGF1/PRC1 targeting, an exon that encodes most of the KDM2B ZF-CxxC domain and is shared by both the long and short form of the protein was flanked by loxP sites (Kdm2bfl/fl). Homozygous mouse ES cell lines were derived that also stably express a tamoxifen inducible form of CRE-recombinase. CRE induced deletion of the ZF-CxxC domain by the addition of tamoxifen yields KDM2B long and short form proteins that are incapable of binding to CpG island DNA but still remain associated with the PCGF1/PRC1 variant complex. We then assessed genome-wide occupancy of the PRC1 component RING1B and the PRC2 component SUZ12 to examine the impact of losing KDM2B-dependent targeting of polycomb. KDM2Bfl/fl ES cells were treated with 800M-BM-5M tamoxifen for 72hours and compared to untreated control cells by ChIP-seq for KDM2B, RING1B and SUZ12, and RNA-seq.
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2013-02-20 | E-GEOD-41314 | biostudies-arrayexpress
Project description:The chromatin modifying activities inherent to polycomb repressive complexes PRC1 and PRC2 play an essential role in gene regulation, cellular differentiation, and development. However, the mechanisms by which these complexes recognize their target sites and function together to form repressive chromatin domains remain poorly understood. Recruitment of PRC1 to target sites has been proposed to occur through a hierarchical process, dependent on the prior nucleation of PRC2 and placement of H3K27me3. Here, using a de novo targeting assay in mouse embryonic stem cells we unexpectedly discover that PRC1-dependent H2AK119ub1 leads to the recruitment of PRC2 and H3K27me3 to effectively initiate a polycomb domain. Genetic ablation of catalytic subunit of the PRC1 complex (RINGA/B) and ChIP-seq analysis of PRC1 and PRC2 components confirmed genome-wide decreases in PRC2 occupancy and H3K27me3 levels at PRC target sites. This activity is restricted to variant PRC1 complexes and genetic ablation experiments reveal that targeting of the variant PCGF1/PRC1 complex by KDM2B to CpG islands is required for polycomb domain formation and normal development. Together these observations provide a surprising new PRC1-dependent logic for PRC2 occupancy and polycomb domain formation. RING1A-/-;RING1Bfl/fl ES cells were treated with 800M-BM-5M tamoxifen for 48hours and compared to untreated control cells by ChIP-seq for RING1B, SUZ12, EZH2 and H3K27me3.
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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.
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Project description:CpG island elements are associated with most mammalian gene promoters, yet how they contribute to gene regulation remains poorly understood. Recently it has become clear that a subset of CpG islands in embryonic stem cells can act as polycomb response elements and are recognized by the polycomb silencing systems to regulate the expression of genes involved in pluripotency and early developmental transcription programs. How CpG islands function mechanistically as nucleation sites for polycomb repressive complexes remains unknown. Here we discover that the KDM2B protein, by virtue of its ZF-CxxC DNA binding domain, specifically recognizes non-methylated DNA in CpG islands elements genome-wide. Through a physical interaction with the polycomb repressive complex 1 (PRC1), KDM2B targets PRC1 to CpG islands where it contributes to H2AK119ub1 and gene repression at a subset of polycomb targets. Unexpectedly, we also find that CpG islands are occupied by low levels of PRC1 throughout the genome, suggesting that the KDM2B-PRC1 complex may sample CpG island associated genes for susceptibility to polycomb mediated silencing. These observations demonstrate an unexpected and direct link between recognition of CpG islands by KDM2B and targeting of the polycomb repressive system. This provides the basis for a new model describing the functionality of CpG islands as mammalian PREs. ChIP-Seq to compare KDM2A vs. KDM2B genome-wide binding profiles and to understand the contribution of KDM2B to RING1B nucleation. Binding of Kdm2a and Kdm2b to the genome was examined in wildtype mESC, and Kdm2b and Ring1b in mESC where Kdm2b has been stably knocked down by shRNA.
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