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DDX5-deficient affect cell fate decision by regulating lineage specific genes and polycomb repressive complexes [RNA-seq]

ABSTRACT: RNA-binding proteins (RBPs) are involved in a wide variety of regulatory pathways in mammalian cells. Here, we report that the DEAD-box RBP DDX5 (also known as p68) inhibits induced pluripotency by negatively regulating the expression and function of a non-canonical polycomb complex 1 (PRC1) subunit, RYBP, by modulating microRNA-125b processing. DDX5 loss-of-function, both during reprogramming and the somatic to pluripotent transition, and also in the differentiation of mouse embryonic stem cells, results in the suppression of lineage-specific genes via an RYBP-dependent ubiquitination of histone H2A at K119 (H2AK119ub1). RYBP functions as both transcriptional repressor through PRC1 but also as an activator through its interaction with OCT4 during reprogramming. Diminished DDX5 also potentiates RYBP-mediated recruitment of OCT4 to the promoter of the pluripotency activation gene Kdm2b. These data show that DDX5 down-regulation stimulates silencing of lineage-specific genes by RYBP-PRC1 in the early phase of reprogramming and activation of the pluripotency gene network by RYBP-OCT4 in the later phase of reprogramming.

ORGANISM(S): Mus musculus

PROVIDER: GSE76824 | GEO | 2017/01/22

SECONDARY ACCESSION(S): PRJNA308722

REPOSITORIES: GEO

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Similar Datasets

DDX5-deficient affect cell fate decision by regulating lineage specific genes and polycomb repressive complexes [miRNA-seq]

Project description:RNA-binding proteins (RBPs) are involved in a wide variety of regulatory pathways in mammalian cells. Here, we report that the DEAD-box RBP DDX5 (also known as p68) inhibits induced pluripotency by negatively regulating the expression and function of a non-canonical polycomb complex 1 (PRC1) subunit, RYBP, by modulating microRNA-125b processing. DDX5 loss-of-function, both during reprogramming and the somatic to pluripotent transition, and also in the differentiation of mouse embryonic stem cells, results in the suppression of lineage-specific genes via an RYBP-dependent ubiquitination of histone H2A at K119 (H2AK119ub1). RYBP functions as both transcriptional repressor through PRC1 but also as an activator through its interaction with OCT4 during reprogramming. Diminished DDX5 also potentiates RYBP-mediated recruitment of OCT4 to the promoter of the pluripotency activation gene Kdm2b. These data show that DDX5 down-regulation stimulates silencing of lineage-specific genes by RYBP-PRC1 in the early phase of reprogramming and activation of the pluripotency gene network by RYBP-OCT4 in the later phase of reprogramming.

2017-01-22 | GSE89690 | GEO

DDX5-deficiency affects cell fate decisions by regulating lineage specific genes and polycomb repressive complexes

2017-01-22 | GSE76823 | GEO

Kdm2b regulates somatic reprogramming through variant PRC1 complex dependent function [RNA-seq]

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

Kdm2b regulates somatic reprogramming through variant PRC1 complex dependent function [ChIP-seq, MeDIP-seq]

2017-11-19 | GSE93972 | GEO

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 [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]

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

Functional dissection of PRC1 subunits RYBP and YAF2 during neural differentiation of embryonic stem cells

Project description:Polycomb repressive complex 1 (PRC1) comprises two different complexes: CBX-containing canonical PRC1 (cPRC1) and RYBP/YAF2-containing variant PRC1 (vPRC1). RYBP and its paralog YAF2 recruit vPRC1 to catalyze H2AK119ub through a positive-feedback model. Here, we show that expression of RYBP and YAF2 decreases and increases, respectively, during neural differentiation of embryonic stem cells (ESCs). Rybp knockout impairs neural differentiation by activating Wnt signaling and derepressing nonneuroectoderm-associated genes. However, Yaf2 knockout promotes neural differentiation and leads to redistribution of RYBP binding, increases enrichment of RYBP and H2AK119ub on the RYBP-YAF2 co-targeted genes, and prevents ectopic derepression of nonneuroectoderm-associated genes in neural-differentiated cells. Furthermore, the phase separations mediated by RYBP alone or together with RING1B are easier and more stable than those by YAF2, which might facilitate the deposition of H2AK119ub more abundantly by RYBP-PRC1 than YAF2-PRC1. Together, this study reveals that RYBP might maintain repressed chromatin more strongly and function differentially in regulating mESC neural differentiation compared with YAF2.

2023-10-09 | GSE213413 | GEO

KDM2B binds CpG islands and modulates recruitment of Ring1b

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.

2012-12-26 | E-GEOD-40860 | biostudies-arrayexpress

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