Acetylated histone H3K56 interacts with Oct4 to promote mouse embryonic stem cell pluripotency
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE47387 | GEO | 2013/06/25
SECONDARY ACCESSION(S): PRJNA205391
REPOSITORIES: GEO
Similar Datasets
Project description:The presence of acetylated histone H3K56 in human embryonic stem cells (ESCs) correlates positively with the binding of Nanog, Sox2 and Oct4 (NSO) transcription factors at their target gene promoters. However, the function of H3K56ac there has been unclear. We now report that Oct4 interacts with K56ac and it is functionally important since K56ac combines with NSO factors in ChIP-Seq to mark the regions associated with pluripotency better than NSO alone. Therefore, our data suggest that K56ac plays a critical role in binding to Oct4 to promote the pluripotency of ESCs. Genome wide location analysis ChIP-Seq was performed in mouse embryonic stem cell lines (E14Tg2a) for histone H3K56ac.
2013-06-25 | E-GEOD-47387 | biostudies-arrayexpress
Project description:Oct4 is considered a master transcription factor for pluripotent cell self-renewal and embryo development. It primarily collaborates with other transcriptional factors or coregulators to maintain pluripotency. However, it is still unclear how Oct4 interacts with its partners. Here, we show that the Oct4 linker interface mediates competing and balanced Oct4 protein interactions which are crucial for maintaining pluripotency. Linker mutant ESCs maintain the key pluripotency genes expression, but show decreased expression of self-renewal genes and increased expression of differentiation genes which result in impaired ESCs self-renewal and early embryonic lethality. Linker mutation dose not affect Oct4 genomic binding and transactivation potential, but breaks the balanced Oct4 interactome. In mutant ESCs, the interaction between Oct4 and Klf5 was decreased, but interactions between Oct4 and Cbx1, Ctr9, Cdc73 were increased which disrupt the epigenetic state of ESCs. Overexpression of Klf5 or knockdown Cbx1, Cdc73 rescue the cellular phenotype of linker mutant ESCs by rebalancing Oct4 interactome indicating that different partners interact with Oct4 competitively. Thus, by showing how Oct4 interacts with different partners, we provide novel molecular insights to explain how Oct4 contributes to the maintenance of pluripotency.
2021-12-10 | PXD017456 | Pride
Project description:The presence of acetylated histone H3K56 (H3K56ac) in human ES cells (ESCs) correlates positively with the binding of Nanog, Sox2, and Oct4 (NSO) transcription factors at their target gene promoters. However, the function of H3K56ac there has been unclear. We now report that Oct4 interacts with H3K56ac in mouse ESC nuclear extracts and that perturbing H3K56 acetylation decreases Oct4-H3 binding. This interaction is likely to be direct because it can be recapitulated in vitro in an H3K56ac-dependent manner and is functionally important because H3K56ac combines with NSO factors in chromatin immunoprecipitation sequencing to mark the regions associated with pluripotency better than NSO alone. Moreover, reducing H3K56ac by short hairpin Asf1a decreases expression of pluripotency-related markers and increases expression of differentiation-related ones. Therefore, our data suggest that H3K56ac plays a central role in binding to Oct4 to promote the pluripotency of ESCs.
| S-EPMC3710873 | biostudies-literature
Project description:Understanding the molecular underpinnings of pluripotency is a prerequisite for optimal maintenance and application of embryonic stem cells (ESCs). While the protein-protein interactions of core pluripotency factors have been identified in mouse ESCs, their interactome in human ESCs (hESCs) has not to date been explored. Here we mapped the OCT4 interactomes in naïve and primed hESCs, revealing extensive connections to mammalian ATP-dependent nucleosome remodeling complexes.
2021-09-12 | PXD026556 | Pride
Project description:Embryonic stem cell (ESC) pluripotency is governed by a gene regulatory network centred on the transcription factors Oct4 and Nanog. ESCs fluctuate between states of high and low Nanog expression that direct efficient or inefficient self-renewal. To date, robust self-renewing ESC states have only been attained by chemical inhibition of signalling pathways or enforced transgene expression. Here we show that ESCs expressing a reduced range of Oct4 concentrations, typified by Oct4 heterozygous ESCs exhibit stable robust pluripotency. Despite this reduced Oct4 concentration range, this state is characterised by increased genome-wide binding of Oct4, particularly at pluripotency-associated enhancers, homogeneous expression of pluripotency transcription factors, enhanced self-renewal efficiency and delayed differentiation kinetics. In this state, ESCs exhibit increased wnt expression, enhanced LIF-sensitivity, non-responsiveness to FGF signalling and can clonally maintain pluripotency without BMP but remain dependent upon LIF. Robust pluripotency is destabilised either by alteration of the Oct4 level or by removal of LIF. Our findings suggest that robust pluripotency originates from cells with a reduced Oct4 protein concentration and that the wild-type Oct4 range enables effective differentiation.
2013-05-07 | E-MTAB-1617 | biostudies-arrayexpress
Project description:Following DNA replication, the newly reassembled chromatin is disorganized and must mature to its steady state to maintain both genome and epigenome integrity. However, the regulatory mechanisms governing this critical process remain poorly understood. Here, we show that histone H3K56 acetylation (H3K56ac), a mark on newly-synthesized H3, facilitates the remodeling of disorganized nucleosomes in nascent chromatin, and its removal at the subsequent G2/M phase of the cell cycle marks the completion of chromatin maturation. In vitro, H3K56ac enhances the activity of ISWI chromatin remodelers, including yeast ISW1 and its human equivalent SNF2h. In vivo, a deficiency of H3K56ac in nascent chromatin results in the formation of closely packed di-nucleosomes and/or tetra-nucleosomes. In contrast, abnormally high H3K56ac levels disrupt chromatin maturation, leading to genome instability. These findings establish a central role of H3K56ac in chromatin maturation and reveal a mechanism regulating this critical aspect of chromosome replication.
2024-12-02 | GSE269558 | GEO
Project description:Oct4 is considered a master transcription factor for pluripotent cell self-renewal and embryo development. It primarily collaborates with other transcriptional factors or coregulators to maintain pluripotency. However, it is still unclear how Oct4 interacts with its partners. Here, we show that the Oct4 linker interface mediates competing and balanced Oct4 protein interactions which are crucial for maintaining pluripotency. Linker mutant ESCs maintain the key pluripotency genes expression, but show decreased expression of self-renewal genes and increased expression of differentiation genes which result in impaired ESCs self-renewal and early embryonic lethality. Linker mutation dose not affect Oct4 genomic binding and transactivation potential, but breaks the balanced Oct4 interactome. In mutant ESCs, the interaction between Oct4 and Klf5 was decreased, but interactions between Oct4 and Cbx1, Ctr9, Cdc73 were increased which disrupt the epigenetic state of ESCs. Overexpression of Klf5 or knockdown Cbx1, Cdc73 rescue the cellular phenotype of linker mutant ESCs by rebalancing Oct4 interactome indicating that different partners interact with Oct4 competitively. Thus, by showing how Oct4 interacts with different partners, we provide novel molecular insights to explain how Oct4 contributes to the maintenance of pluripotency.
2021-12-10 | GSE144876 | GEO
Project description:Nucleosome dynamics facilitated by histone turnover is required for transcription as well as DNA replication and repair. Histone turnover is often associated with various histone modifications such as H3K56 acetylation (H3K56Ac), H3K36 methylation (H3K36me), and H4K20 methylation (H4K20me). In order to correlate histone modifications and transcription-dependent histone turnover, we performed genome wide analyses for euchromatic regions in G2/M-arrested fission yeast. The results show that transcription-dependent histone turnover at 5’ promoter and 3’ termination regions is directly correlated with the occurrence of H3K56Ac and H4K20 mono-methylation (H4K20me1) in actively transcribed genes. Furthermore, the increase of H3K56Ac and H4K20me1 and antisense RNA production was observed in the absence of the histone H3K36 methyltransferase Set2 and histone deacetylase complex (HDAC) that are involved in the suppression of histone turnover within the coding regions. These results together indicate that H4K20me1 as well as H3K56Ac are bona fide marks for transcription-dependent histone turnover in fission yeast.
2016-06-21 | GSE83538 | GEO
Project description:The transcription factor Oct4/Pou5f1 is a key component of the regulatory circuitry governing pluripotency. Oct4 is also widely used to generate induced pluripotent stem cells (iPSCs) from somatic cells. These observations provide compelling rationale to understand Oct4’s functions. Here we used domain swapping and mutagenesis to compare Oct4’s reprogramming activity with the paralog Oct1/Pou2f1, identifying a redox-sensitive DNA binding domain cysteine residue (Cys48) as a key determinant of both reprogramming and differentiation. In combination with the Oct4 N-terminus, mutating Oct1’s serine at this position to cysteine is sufficient to confer strong reprogramming activity. Conversely, Oct4C48S strongly reduces reprogramming potential. Oct4C48S renders the protein insensitive to oxidative inhibition of DNA binding. The same mutation prevents oxidation-mediated protein ubiquitylation. An engineered Pou5f1C48S point mutation has little effect on undifferentiated cells embryonic stem cells (ESCs), but upon retinoic acid (RA)-mediated differentiation causes retention of Oct4 expression, decreased proliferation, and increased apoptosis. Transcriptional profiling reveals that the retention of pluripotency also manifests at the RNA level. Pou5f1C48S ESCs also contribute poorly to adult somatic tissues and form less differentiated teratomas. Collectively, the data support a model in which Oct4 redox sensing is a positive reprogramming determinant during one or more reprogramming steps, and mediates Oct4 degradation during differentiation.
2024-04-09 | GSE241332 | GEO
Project description:We combine a genome-scale RNAi screen in mouse epiblast stem cells (EpiSCs) with genetic interaction, protein localization and “protein-level dependency” studies – a systematic technique that uncovers post-transcriptional regulation – to delineate the network of factors that control the expression of Oct4, a key regulator of pluripotency. Our data signify that there are similarities, but also fundamental differences in Oct4 regulation in EpiSCs vs. embryonic stem cells (ESCs). Through multiparametric data analyses we predict that Tox4 is associating with the Paf1C complex, which maintains cell identity in both cell types and validate that this protein-protein interaction exists in ESCs and EpiSCs. We also identify numerous knockdowns that increase Oct4 expression in EpiSCs, indicating that, in stark contrast to ESCs, Oct4 is under active repressive control in EpiSCs. These studies provide a framework for better understanding pluripotency and for dissecting the molecular events that govern the transition from the pre-implantation to the post-implantation state.
2015-08-07 | GSE62357 | GEO