Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

RBBP4 regulates pluripotent-to-2C-like state transition through modulating heterochromatin assembly (ChIP-Seq)

ABSTRACT: Cellular totipotency is critical for generating a whole organism, yet how to establish totipotency is still poorly illustrated. Unlike pluripotent stem cells, abundant transposable elements (TEs) are activated in the totipotent cells. Here, we show that histone chaperone RBBP4 but not its homologous RBBP7 is indispensable in maintaining the identity of mouse embryonic stem cells (mESCs). Auxin-induced degradation of RBBP4, but not RBBP7, reprograms pluripotent state to a totipotent-like (also known as 2C-like) state. Mechanistically, RBBP4 could recruit G9a and KAP1 to bind on retrotransposons, especially endogenous retroviruses. RBBP4 degradation reduces the binding of G9a-mediated H3K9me2 on ERVL (particularly MERVL) and KAP1-mediated H3K9me3 on ERV1/ERVK, respectively. Moreover, RBBP4 facilitates nucleosome occupancy through chromatin remodeler CHD4 and RBBP4 depletion leads to attenuation of CHD4 binding and nucleosome occupancy on TEs. Together, our study reveals the important roles of RBBP4 in heterochromatin assembly and its loss activates TEs in mESCs, opening a new way to obtain totipotent cells in vitro.

ORGANISM(S): Mus musculus

PROVIDER: GSE218652 | GEO | 2023/03/15

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

RBBP4 regulates pluripotent-to-2C-like state transition through modulating heterochromatin assembly (Mnase-Seq)

Project description:Cellular totipotency is critical for generating a whole organism, yet how to establish totipotency is still poorly illustrated. Unlike pluripotent stem cells, abundant transposable elements (TEs) are activated in the totipotent cells. Here, we show that histone chaperone RBBP4 but not its homologous RBBP7 is indispensable in maintaining the identity of mouse embryonic stem cells (mESCs). Auxin-induced degradation of RBBP4, but not RBBP7, reprograms pluripotent state to a totipotent-like (also known as 2C-like) state. Mechanistically, RBBP4 could recruit G9a and KAP1 to bind on retrotransposons, especially endogenous retroviruses. RBBP4 degradation reduces the binding of G9a-mediated H3K9me2 on ERVL (particularly MERVL) and KAP1-mediated H3K9me3 on ERV1/ERVK, respectively. Moreover, RBBP4 facilitates nucleosome occupancy through chromatin remodeler CHD4 and RBBP4 depletion leads to attenuation of CHD4 binding and nucleosome occupancy on TEs. Together, our study reveals the important roles of RBBP4 in heterochromatin assembly and its loss activates TEs in mESCs, opening a new way to obtain totipotent cells in vitro.

2023-03-15 | GSE218655 | GEO

RBBP4 regulates pluripotent-to-2C-like state transition through modulating heterochromatin assembly (CUT&Tag)

2023-03-15 | GSE218654 | GEO

RBBP4 is an epigenetic barrier for inducing pluripotent stem cells to totipotent 2C-like cells [scRNA-seq]

2023-03-15 | GSE221555 | GEO

RBBP4 is an epigenetic barrier for inducing pluripotent stem cells to totipotent 2C-like cells [RNA-seq]

2023-03-15 | GSE221554 | GEO

RBBP4 regulates pluripotent-to-2C-like state transition through modulating heterochromatin assembly (CUT&RUN)

2023-03-15 | GSE218653 | GEO

RBBP4 regulates pluripotent-to-2C-like state transition through modulating heterochromatin assembly (RNA-Seq)

2023-03-15 | GSE218651 | GEO

Individual retrotransposon integrants are differentially controlled by KZFP/KAP1-dependent histone methylation, DNA methylation and TET-mediated hydroxymethylation in naïve embryonic stem cells

Project description:The KZFP/KAP1 (KRAB zinc finger proteins/KRAB-associated protein 1) system plays a central role in the silencing of transposable elements (TEs) and the maintenance of parent-of-origin DNA methylation at imprinting control regions (ICRs) during the wave of genome-wide reprogramming that precedes implantation. In naïve murine embryonic stem cells (mESCs), the genome is maintained highly hypomethylated by a combination of active demethylation (operated by TET proteins) and lack of de novo methylation; in these cells, KAP1 is tethered by sequence-specific KZFPs to ICRs and TEs where it recruits histone and DNA methyltransferases to impose heterochromatin formation and DNA methylation. Here, upon removing either KAP1 or the cognate KZFP, we observed rapid TET-dependent accumulation of 5hmC at both ICRs and TEs. In absence of the KZFP/KAP1 complex, ICRs lost heterochromatic histone marks and underwent both active and passive DNA demethylation. Using RNA-seq, we further compared the expression profiles of TEs upon Kap1 removal in wild type, Dnmt and Tet triple knockout mESCs. We found that KAP1 represents the main effector of TEs repression in all three settings, yet we could additionally identify specific groups of TEs also controlled by DNA methylation. Furthermore, activation upon Kap1 removal in the absence of TET proteins could be either blunted or increased depending on TE subsets, indicating a complex interplay between heterochomatin and active demethylation in regulating the expression of the endovirome.

2018-02-28 | GSE95720 | GEO

Dux cluster duplication ensures fully activation of totipotent genes

Project description:Mammalian zygotic genome activation (ZGA) following fertilization refers to the process that results in transcriptional awakening of the embryonic genome at two-cell (2C) stage in mice or 4-8 cell stage in human. ZGA confers to the mouse 2C embryo a unique transcriptional profile characterized by transient up-regulation of many totipotency-related genes and MERVL transposons. Intriguingly, many ZGA-related totipotent genes are duplicated and clustered in the genome during evolution, including Dux cluster, OBOX and Zscan4 family members in mice. Yet, the contribution and biological significance of the totipotency-related gene duplication events during evolution in totipotency acquisition remain poorly understood. Here, we focus on Dux cluster, the master regulator of ZGA that is necessary and sufficient for the emergence of 2C-like cells (2CLCs) and activation of target totipotent genes in mouse embryonic stem cells (ESCs). By reducing Dux gene copy number from 31 to 0 or 1 with CRISPR-Cas9 technology, we generated Dux-KO and Dux (n=1) ES cell lines, respectively. We found that the totipotent gene transcriptional profile could not be fully activated in Dux (n=1) mESCs compared to wild type (WT) mESCs after treatment with DNMT1 protein degrader, mimicking the DNA demethylation process during early embryo development. These data demonstrate that Dux cluster duplication is essential for fully activation of totipotency-related genes, ensuring ZGA and totipotency acquisition.

2024-10-12 | GSE263217 | GEO

Unbiased in vivo exploration of nuclear bodies-enhanced sumoylation reveals that PML orchestrates embryonic stem cell fate (II)

Project description:Membrane-less organelles are condensates formed by phase separation whose functions often remain enigmatic. Upon oxidative stress, PML scaffolds Nuclear Bodies (NBs) to regulate senescence or metabolic adaptation, but their role in pluripotency remains elusive. Here we establish that PML is required for basal SUMO2/3 conjugation in mESCs and oxidative stress-driven sumoylation in mESCs or in vivo. PML NBs create an oxidationprotective environment for UBC9-driven SUMO2/3 conjugation of PML partners, often followed by their poly-ubiquitination and degradation. Differential in vivo proteomics identified several members of the KAP1 complex as PML NB-dependent SUMO2-targets. The latter drives functional activation of this key epigenetic repressor. Accordingly, Pml-/- mESCs reexpress transposable elements and display features of totipotent-like cells, a process further enforced by PML-controlled SUMO2-conjugation of DPPA2. Finally, PML is required for adaptive stress responses in mESCs. Collectively, PML orchestrates mESC fate through SUMO2-conjugation of key transcriptional or epigenetic regulators, raising new mechanistic hypotheses about PML roles in normal or cancer stem cells.

2023-03-06 | PXD032240 | Pride

Unbiased in vivo exploration of nuclear bodies-enhanced sumoylation reveals that PML orchestrates embryonic stem cell fate

2022-09-14 | PXD028865 | Pride