Trps1 regulates mouse zygotic genome activation and preimplantation embryo development via the PDE4D/AKT/CREB signaling pathway
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PROVIDER: PRJNA1196330 | ENA |
REPOSITORIES: ENA
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Project description:Despite zygotic genome activation (ZGA) is crucial for early embryonic development, its regulatory mechanism is still unclear in mammals. In the present study, we demonstrate that TRPS1, a maternal factor, plays an essential role in mouse early embryogenesis by regulating the transition from 2-cell to 4-cell embryos during preimplantation development. The absence of Trps1 could leads to impaired ZGA through AKT/CREB signaling pathway. Furthermore, our findings suggest that TRPS1 may modulate the transcription of Pde4d to influence AKT and CREB phosphorylation. Interestingly, compared to Trps1 knockdown alone, co-injection of Trps1 siRNA and Pde4d mRNA significantly enhances the development rate of 4-cell embryos. Collectively, these results indicate a negative involvement of Trps1 in mouse preimplantation embryo development by targeting the PDE4D/AKT/CREB pathway to regulate ZGA.
2024-12-15 | GSE283924 | GEO
Project description:How maternal factors in oocytes initiate zygotic genome activation (ZGA) remains elusive. Recent studies indicate that DPPA2 and DPPA4 are required for establishing a 2-cell embryo-like (2C-like) state in mouse embryonic stem cells (ESCs) in a DUX-dependent manner. These results suggest that DPPA2 and DPPA4 are essential maternal factors that regulate Dux and ZGA in embryos. By analyzing maternal knockout and maternal-zygotic knockout embryos, we unexpectedly found that Dux activation, ZGA, and preimplantation development are normal in embryos without DPPA2 or DPPA4. Thus, unlike in ESCs/2C-like cells, DPPA2 and DPPA4 are dispensable for ZGA and preimplantation development.
2021-12-06 | GSE181723 | GEO
Project description:Mutations in TRPS1 cause trichorhinophalangeal syndrome types I and III, which are characterized by sparse scalp hair in addition to craniofacial and skeletal abnormalities. Trps1 is a vertebrate transcription factor containing nine zinc-finger domains, including a GATA-type zinc finger through which it binds DNA. Mice in which the GATA domain of Trps1 has been deleted (Trps1∆gt/∆gt) have a reduced number of pelage follicles and lack vibrissae follicles postnatally. To identify the transcriptional targets of Trps1 in the developing vibrissa follicle, we performed microarray hybridization analysis comparing expression patterns in the whisker pads of wild-type versus Trps1∆gt/∆gt embryos. We identified a number of transcription factors and Wnt inhibitors among transcripts downregulated in the mutant embryos, and several extracellular matrix proteins there were upregulated in the mutant samples. Whole whisker pads were dissected from E12.5 embryos and total RNA was isolated using the RNeasy Mini Kit (Qiagen). Triplicate RNA samples from three independent embryos of each genotype were amplified and labeled for hybridization to Affymetrix GeneChip MOE430A microarrays using Affymetrix reagents and protocols. The data output was analyzed using GeneSpring GX 10.0 commercial software (Agilent Technologies). P-values were calculated using an unpaired t-test. Expression values with a p-value less than or equal to 0.05 and a fold difference of at least 1.5 relative to wild-type baseline expression levels were considered significant.
2011-12-22 | E-GEOD-33766 | biostudies-arrayexpress
Project description:TRPS1 was recently identified as a radiation marker in breast cancer. In order to characterise the molecular phenotype that is associated with TRPS1 we knocked out the gene in two radiation-transformed breast cell lines.
2017-10-01 | E-MTAB-6008 | biostudies-arrayexpress
Project description:The cornea is a transparent organ, highly specialized and unique that is continually subjected to abrasive forces and occasional mechanical or chemical trauma because of its anatomical localization. Upon injury, the extracellular matrix (ECM) rapidly changes to promote wound healing through integrin-dependent activation of specific signal transduction mediators whose contribution is to favor faster closure of the wound by altering the adhesive and migratory properties of the cells surrounding the damaged area. In this study, we exploited the human tissue-engineered cornea (hTECs) as a model to study the signal transduction pathways that participate to corneal wound healing. By exploiting both gene profiling and activated kinases arrays, we could demonstrate the occurrence of important alterations in the level of expression and activation of a few mediators from the PI3K/Akt and CREB pathways in response to the ECM remodeling taking place during wound healing of damaged hTECs. Pharmacological inhibition of CREB with C646 considerably accelerated wound closure compared to controls. This process was considerably accelerated further when both C646 and SC79, an Akt agonist, were added together to wounded hTECs. Therefore, our study demonstrate that proper corneal wound healing requires the activation of Akt together with the inhibition of CREB and that wound healing in vitro can be altered by the use of pharmacological inhibitors (such as C646) or agonists (such as SC79) of these mediators.
2018-04-21 | GSE113438 | GEO
Project description:Mutations in TRPS1 cause trichorhinophalangeal syndrome types I and III, which are characterized by sparse scalp hair in addition to craniofacial and skeletal abnormalities. Trps1 is a vertebrate transcription factor containing nine zinc-finger domains, including a GATA-type zinc finger through which it binds DNA. Mice in which the GATA domain of Trps1 has been deleted (Trps1∆gt/∆gt) have a reduced number of pelage follicles and lack vibrissae follicles postnatally. To identify the transcriptional targets of Trps1 in the developing vibrissa follicle, we performed microarray hybridization analysis comparing expression patterns in the whisker pads of wild-type versus Trps1∆gt/∆gt embryos. We identified a number of transcription factors and Wnt inhibitors among transcripts downregulated in the mutant embryos, and several extracellular matrix proteins there were upregulated in the mutant samples.
2011-12-22 | GSE33766 | GEO
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:We report here the analysis of TRPS1 chromatin binding by ChIP-Seq in embryonal rhabdomyosarcoma RD cells. We use here parental and TRPS1-KO RD cells. RD cells and RD-TRPS1-KO cells were cultured in growth medium and chromatin was prepared. TRPS1 DNA binding in RD cells and RD-TRPS1-KO cells using a selfmade antibody (referenced in Elster et al.) was determined by ChIP-seq.
2023-07-24 | GSE197550 | GEO
Project description:TRPS1 was selected as a candidate for further exploring the molecular mechanism of CRC distant metastasis according to single cell seq results. We next performed bulk RNA sequencing to explore the underlying mechanism by which TRPS1 R544Q mutation contributes to CRC metastasis.Comparative gene expression profiling analysis of RNA-seq data for HCT116 (control,TRPS1,R544Q）and SW480 (control,TRPS1,R544Q）
2023-12-15 | GSE206729 | GEO
Project description:The molecular etiology underlying TRPS1 loss-of-function in tricho-rhino-phalangeal syndrome (TRPS) remains to be understood. Intriguingly, TRPS1 is also bioinformatically postulated as a breast cancer driver. We report here that TRPS1 is prevalently amplified in breast cancer and promotes breast carcinogenesis. We showed that the tumorigenic potential of TRPS1 is derived from its nucleation of the replication machinery and its enforced replication of H3K9me3-marked heterochromatic regions. During early stage of genome duplication, TRPS1 encourages chromatin loading of the anaphase-promoting complex (APC/C) and subsequent degradation of Geminin, an inhibitor for the assembly of the pre-replication complex, leading to uncontrolled refiring of the heterochromatic replication origins. Overexpression of wild-type but not TRPS-associated loss-of-function mutants of TRPS1 is sufficient to drive genome amplification that mimics the genomic alterations in cancer, and TRPS1-evoked aberrant genome dynamically evolves to confer therapeutic resistance to a broad spectrum of treatment compounds. Together, these results link TRPS1 to heterochromatin replication, highlighting the sufficiency of a single oncogene to drive cancer genome evolution.
2021-08-16 | GSE118643 | GEO