Hippo-YAP signaling controls lineage differentiation of mouse embryonic stem cells through modulating the formation of super-enhancers
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ABSTRACT:
PROVIDER: PRJNA532585 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR10992251_1.fastq.gz | Fastqsanger.gz | |||
| SRR10992251_2.fastq.gz | Fastqsanger.gz | |||
| SRR10992252_1.fastq.gz | Fastqsanger.gz | |||
| SRR10992252_2.fastq.gz | Fastqsanger.gz | |||
| SRR10992253_1.fastq.gz | Fastqsanger.gz |
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Project description:Hippo-YAP signaling pathway is a highly conserved pathway during evolution. It involves in a broad spectrum of physiological and pathological procedure. It also functions in early lineage differentiation of pluripotent stem cells, but the detailed mechanisms remain elusive. Our previous research revealed that knockout of Mst1 and Mst2, the key components of Hippo signaling in mouse embryonic stem cells (ESCs), led ESCs preferentially differentiate into ectoderm lineage, and the differentiation to mesoderm and endoderm lineage was disturbed. To uncover the underlying regulatory mechanisms, we performed ChIP-seq experiments with antibodies against Yap, master transcription factors and some characterized histone modification markers. Combined with RNA-seq assays of wild type and Mst KO ESCs and day 4 embryoid bodies (EBs), we found that YAP is preferentially enriched at Nanog, Sox2, Oct4 and H3K27Ac co-marked super-enhancers (SEs) in ESCs. The upregulation of YAP in Mst KO ESCs resulted in the formation of new super-enhancers on lineage associated genes, leading to the upregulation of these genes and the distortion of ESC differentiation. Hence, our study revealed a super-enhancer related ESC lineage differentiation mechanism which can be shaped by Hippo-YAP signaling.
2020-05-24 | GSE144579 | GEO
Project description:Hippo-YAP signaling pathway is a highly conserved pathway during evolution. It involves in a broad spectrum of physiological and pathological procedure. It also functions in early lineage differentiation of pluripotent stem cells, but the detailed mechanisms remain elusive. Our previous research revealed that knockout of Mst1 and Mst2, the key components of Hippo signaling in mouse embryonic stem cells (ESCs), led ESCs preferentially differentiate into ectoderm lineage, and the differentiation to mesoderm and endoderm lineage was disturbed. To uncover the underlying regulatory mechanisms, we performed ChIP-seq experiments with antibodies against Yap, master transcription factors and some characterized histone modification markers. Combined with RNA-seq assays of wild type and Mst KO ESCs and day 4 embryoid bodies (EBs), we found that YAP is preferentially enriched at Nanog, Sox2, Oct4 and H3K27Ac co-marked super-enhancers (SEs) in ESCs. The upregulation of YAP in Mst KO ESCs resulted in the formation of new super-enhancers on lineage associated genes, leading to the upregulation of these genes and the distortion of ESC differentiation. Hence, our study revealed a super-enhancer related ESC lineage differentiation mechanism which can be shaped by Hippo-YAP signaling.
2020-05-24 | GSE144578 | GEO
Project description:Hippo-YAP signaling pathway is a highly conserved pathway during evolution. It involves in a broad spectrum of physiological and pathological procedure. It also functions in early lineage differentiation of pluripotent stem cells, but the detailed mechanisms remain elusive. Our previous research revealed that knockout of Mst1 and Mst2, the key components of Hippo signaling in mouse embryonic stem cells (ESCs), led ESCs preferentially differentiate into ectoderm lineage, and the differentiation to mesoderm and endoderm lineage was disturbed. To uncover the underlying regulatory mechanisms, we performed ChIP-seq experiments with antibodies against Yap, master transcription factors and some characterized histone modification markers. Combined with RNA-seq assays of wild type and Mst KO ESCs and day 4 embryoid bodies (EBs), we found that YAP is preferentially enriched at Nanog, Sox2, Oct4 and H3K27Ac co-marked super-enhancers (SEs) in ESCs. The upregulation of YAP in Mst KO ESCs resulted in the formation of new super-enhancers on lineage associated genes, leading to the upregulation of these genes and the distortion of ESC differentiation. Hence, our study revealed a super-enhancer related ESC lineage differentiation mechanism which can be shaped by Hippo-YAP signaling.
2020-05-24 | GSE144577 | GEO
Project description:Hippo-YAP signaling controls lineage differentiation of mouse embryonic stem cell through super-enhancers [RNA-seq]
| PRJNA604041 | ENA
Project description:Hippo-YAP signaling controls lineage differentiation of mouse embryonic stem cell through super-enhancers [ChIP-seq 1]
| PRJNA604043 | ENA
Project description:Hippo-YAP signaling controls lineage differentiation of mouse embryonic stem cell through super-enhancers [ChIP-seq 2]
| PRJNA604042 | ENA
Project description:Splicing dysregulations extensively occur in cancers, yet the biological consequences of such alterations are mostly undefined. Here we report that the Hippo-YAP signaling, a key pathway that regulates cell proliferation and organ size, is under control of a new splicing switch. We show that TEAD4, the transcription factor that mediates Hippo-YAP signaling, undergoes alternative splicing facilitated by the tumor suppressor RBM4, producing a truncated isoform, TEAD4-S, which lacks N-terminal DNA-binding domain but maintains YAP-interaction domain. TEAD4-S is located in both nucleus and cytoplasm, acting as a dominant negative isoform to YAP activity. Consistently, TEAD4-S is reduced in cancer cells, and its re-expression suppresses cancer cell proliferation and migration, inhibiting tumor growth in xenograft mouse model. Furthermore, TEAD4-S is reduced in human cancers, and patients with elevated TEAD4-S levels have improved survival. Altogether these data reveal a novel RBM4-mediated splicing switch that serves to fine-tune Hippo-YAP pathway. Cell lines stably expressing YAP, YAP/TEAD4-S, YAP/TEAD4-FL, YAP/RBM4 and control vector were created, and the total RNA was purified from the cells using TRIzol reagents. The polyadenylated RNAs were purified for construction of sequencing library using kapa TruSeq Total RNA Sample Prep kits (UNC High Throughput Sequencing Facility).
2016-06-16 | E-GEOD-80372 | biostudies-arrayexpress
Project description:Yes-associated protein (YAP), the downstream transducer of the Hippo pathway is a key regulator of organ size, differentiation and tumourigenesis. Yet, the activity of YAP can also be modulated by Hippo-independent functions. To disclose these Hippo-independent regulators, we performed a genome-wide CRISPR screening approach that identified the transcriptional repressor protein Trichorhinophalangeal Syndrome 1 (TRPS1) as a potent repressor of YAP-dependent transactivation. Using RNA-Sequencing and ChIP-Sequencing approaches we show that TRPS1 globally regulates YAP-dependent transcription by binding to a large set of joint genomic sites, mainly enhancers. Mechanistically, TRPS1 represses YAP-dependent enhancers function by recruiting a spectrum of corepressor complexes to joint sites. Consequently, loss of TRPS1 leads to activation of enhancers due to increased H3K27 acetylation and an altered promoter-enhancer interaction landscape. TRPS1 is commonly amplified in breast cancer which is associated decreased YAP activity and leads to a decreased frequency of intratumoural immune cells. Consistently, depletion of TRPS1 in the syngeneic 4T1 tumour model leads to a strongly decreased tumour growth in vivo. Our study uncovers TRPS1 as a new epigenetic regulator of YAP activity and it connects repression of YAP-dependent enhancer function to breast cancer. For project-related queries, please contact bjoern.voneyss@leibniz-fli.de <mailto:bjoern.voneyss@leibniz-fli.de>.
2018-08-09 | PXD009819 | Pride
Project description:The Hippo pathway functions as a tumor-suppressor pathway in human cancers, while the dys-function of Hippo pathway is frequently observed in malignancies. Although the YAP/TAZ activity is tightly controlled by the phosphorylation cascade of MST-LATS-YAP/TAZ axis, it is still unclear why YAP/TAZ protein is activated in human cancers, even Hippo pathway is still active. Besides phosphorylation, recent studies implicate that several post-translational modifications also play critical roles in modulating TAZ function, including ubiquitination. Here, by a DUB (Deubiquitinases) siRNA screening library, we discovered DUB1 as a critical modulator to facilitate gastric cancer stemness and progression, which deubiquitinated and activated TAZ protein. We also identified DUB1 was elevated in gastric cancer, which correlated with TAZ activation and poor survival. DUB1 associated with TAZ protein and deubiquitinated TAZ at several lysine sites, which subsequently stabilized and facilitated TAZ function. Our study revealed a novel deubiquitinase of Hippo/TAZ axis and one possible therapeutic target for Hippo-driven gastric cancer.
2022-02-12 | GSE196262 | GEO
Project description:The Hippo/YAP signaling pathway is a crucial regulator of tissue growth and stem cell activity.YAP, a transcriptional co-activator and main effector of the pathway, is also a powerful driver of tumorigenesis However, the genetic program regulated by YAP and the mechanism by which YAP controls transcription remains to be fully elucidated. Here, we utilize global chromatin occupancy analyses to demonstrate that robust YAP binding is restricted to a relatively small number of distal regulatory elements in the genome. YAP-occupancy defines a subset of enhancers and super-enhancers with the highest transcriptional outputs. We find that YAP modulates transcription from these elements predominantly by regulating promoter-proximal Polymerase II (PolII) pause release. Mechanistically, YAP physically interacts and recruits the Mediator complex to enhancers, which then allows for recruitment of the CDK9 elongating kinase. Genetic and chemical perturbation experiments demonstrate the requirement for Mediator and CDK9 in YAP-driven phenotypes of overgrowth and tumorigenesis. Our results here uncover the molecular mechanisms employed by YAP to exert its growth and oncogenic functions, and suggest new strategies for intervention.
2015-10-01 | GSE68296 | GEO