Similar Datasets
Project description:YAP and TAZ protect against white adipocyte cell death during obesity
| PRJNA577719 | ENA
Project description:The expansion of the white adipose tissue (WAT) in obesity goes along with increased mechanical, metabolic and inflammatory stress. How adipocytes resist this stress is still poorly understood. Both in human and mouse adipocytes, the transcriptional co-activators YAP/TAZ and YAP/TAZ target genes become activated during obesity. When fed a high-fat diet (HFD), mice lacking YAP/TAZ in white adipocytes develop severe lipodystrophy with adipocyte cell death. The pro-apoptotic factor BIM, which is downregulated in adipocytes of obese mice and humans, is strongly upregulated in YAP/TAZ-deficient adipocytes under HFD, and suppression of BIM expression reduces adipocyte apoptosis. In differentiated adipocytes, TNFα and IL-1β promote YAP/TAZ nuclear translocation via activation of RhoA-mediated actomyosin contractility and increase YAP/TAZ-mediated transcriptional regulation by activation of c-Jun N-terminal kinase (JNK) and AP-1. Our data indicate that the YAP/TAZ signaling pathway may be a target to control adipocyte cell death and compensatory adipogenesis during obesity.
| S-EPMC7595161 | biostudies-literature
Project description:The transcriptional coregulators YAP and TAZ control tissue homeostasis as downstream effectors of the Hippo signaling pathway. The molecular mechanisms by which they regulate cell differentiation or dedifferentiation have remained unclear, however. Here we reveal how YAP/TAZ regulates the transcription and genomic activity of the adipocyte lineage-specification factor PPARγ at the chromatin level. TAZ binds to the Pparg2 genomic region and to PPARγ target gene enhancers, thereby inducing chromatin reprogramming and transcriptional repression. Binding to TEAD transcription factors is essential for this repressive action of TAZ, but direct protein interaction with PPARγ via the WW domain of TAZ is not. Single-nucleus genomic analyses of mouse adipose tissue revealed that YAP/TAZ hyperactivation drives extensive epigenetic changes and the dedifferentiation of adipocytes. Collectively, our findings indicate that YAP/TAZ determine adipocyte fate by modulating the expression of a key transcription factor and the enhancer landscape of its target genes.
2025-12-16 | GSE277188 | GEO
Project description:The transcriptional coregulators YAP and TAZ control tissue homeostasis as downstream effectors of the Hippo signaling pathway. The molecular mechanisms by which they regulate cell differentiation or dedifferentiation have remained unclear, however. Here we reveal how YAP/TAZ regulates the transcription and genomic activity of the adipocyte lineage-specification factor PPARγ at the chromatin level. TAZ binds to the Pparg2 genomic region and to PPARγ target gene enhancers, thereby inducing chromatin reprogramming and transcriptional repression. Binding to TEAD transcription factors is essential for this repressive action of TAZ, but direct protein interaction with PPARγ via the WW domain of TAZ is not. Single-nucleus genomic analyses of mouse adipose tissue revealed that YAP/TAZ hyperactivation drives extensive epigenetic changes and the dedifferentiation of adipocytes. Collectively, our findings indicate that YAP/TAZ determine adipocyte fate by modulating the expression of a key transcription factor and the enhancer landscape of its target genes.
2025-12-16 | GSE252503 | GEO
Project description:The transcriptional coregulators YAP and TAZ control tissue homeostasis as downstream effectors of the Hippo signaling pathway. The molecular mechanisms by which they regulate cell differentiation or dedifferentiation have remained unclear, however. Here we reveal how YAP/TAZ regulates the transcription and genomic activity of the adipocyte lineage-specification factor PPARγ at the chromatin level. TAZ binds to the Pparg2 genomic region and to PPARγ target gene enhancers, thereby inducing chromatin reprogramming and transcriptional repression. Binding to TEAD transcription factors is essential for this repressive action of TAZ, but direct protein interaction with PPARγ via the WW domain of TAZ is not. Single-nucleus genomic analyses of mouse adipose tissue revealed that YAP/TAZ hyperactivation drives extensive epigenetic changes and the dedifferentiation of adipocytes. Collectively, our findings indicate that YAP/TAZ determine adipocyte fate by modulating the expression of a key transcription factor and the enhancer landscape of its target genes.
2025-12-16 | GSE277187 | GEO
Project description:The transcriptional coregulators YAP and TAZ control tissue homeostasis as downstream effectors of the Hippo signaling pathway. The molecular mechanisms by which they regulate cell differentiation or dedifferentiation have remained unclear, however. Here we reveal how YAP/TAZ regulates the transcription and genomic activity of the adipocyte lineage-specification factor PPARγ at the chromatin level. TAZ binds to the Pparg2 genomic region and to PPARγ target gene enhancers, thereby inducing chromatin reprogramming and transcriptional repression. Binding to TEAD transcription factors is essential for this repressive action of TAZ, but direct protein interaction with PPARγ via the WW domain of TAZ is not. Single-nucleus genomic analyses of mouse adipose tissue revealed that YAP/TAZ hyperactivation drives extensive epigenetic changes and the dedifferentiation of adipocytes. Collectively, our findings indicate that YAP/TAZ determine adipocyte fate by modulating the expression of a key transcription factor and the enhancer landscape of its target genes.
2025-12-16 | GSE248364 | GEO
Project description:The transcriptional coregulators YAP and TAZ control tissue homeostasis as downstream effectors of the Hippo signaling pathway. The molecular mechanisms by which they regulate cell differentiation or dedifferentiation have remained unclear, however. Here we reveal how YAP/TAZ regulates the transcription and genomic activity of the adipocyte lineage-specification factor PPARγ at the chromatin level. TAZ binds to the Pparg2 genomic region and to PPARγ target gene enhancers, thereby inducing chromatin reprogramming and transcriptional repression. Binding to TEAD transcription factors is essential for this repressive action of TAZ, but direct protein interaction with PPARγ via the WW domain of TAZ is not. Single-nucleus genomic analyses of mouse adipose tissue revealed that YAP/TAZ hyperactivation drives extensive epigenetic changes and the dedifferentiation of adipocytes. Collectively, our findings indicate that YAP/TAZ determine adipocyte fate by modulating the expression of a key transcription factor and the enhancer landscape of its target genes.
2025-12-16 | GSE277190 | GEO
Project description:The transcriptional coregulators YAP and TAZ control tissue homeostasis as downstream effectors of the Hippo signaling pathway. The molecular mechanisms by which they regulate cell differentiation or dedifferentiation have remained unclear, however. Here we reveal how YAP/TAZ regulates the transcription and genomic activity of the adipocyte lineage-specification factor PPARγ at the chromatin level. TAZ binds to the Pparg2 genomic region and to PPARγ target gene enhancers, thereby inducing chromatin reprogramming and transcriptional repression. Binding to TEAD transcription factors is essential for this repressive action of TAZ, but direct protein interaction with PPARγ via the WW domain of TAZ is not. Single-nucleus genomic analyses of mouse adipose tissue revealed that YAP/TAZ hyperactivation drives extensive epigenetic changes and the dedifferentiation of adipocytes. Collectively, our findings indicate that YAP/TAZ determine adipocyte fate by modulating the expression of a key transcription factor and the enhancer landscape of its target genes.
2025-12-16 | GSE277189 | GEO
Project description:The optic vesicle comprises a pool of bi-potential progenitor cells from which the retinal pigment epithelium (RPE) and neural retina fates segregate during ocular morphogenesis. Several transcription factors and signaling pathways have been shown to be important for RPE maintenance and differentiation, but an understanding of the initial fate specification and determination of this ocular cell type is lacking. We show that Yap/Taz-Tead activity is necessary and sufficient for optic vesicle progenitors to adopt RPE identity in zebrafish. A Teadresponsive transgene is expressed within the domain of the optic cup from which RPE arises, and Yap immunoreactivity localizes to the nuclei of prospective RPE cells. yap (yap1) mutants lack a subset of RPE cells and/or exhibit coloboma. Loss of RPE in yap mutants is exacerbated in combination with taz (wwtr1) mutant alleles such that, when Yap and Taz are both absent, optic vesicle progenitor cells completely lose their ability to form RPE. The mechanism of Yap dependent RPE cell type determination is reliant on both nuclear localization of Yap and interaction with a Tead co-factor. In contrast to loss of Yap and Taz, overexpression of either protein within optic vesicle progenitors leads to ectopic pigmentation in a dosagedependent manner. Overall, this study identifies Yap and Taz as key early regulators of RPE genesis and provides a mechanistic framework for understanding the congenital ocular defects of Sveinsson’s chorioretinal atrophy and congenital retinal coloboma. 60 pooled eyes from 36 hpf wild type or vsx2:Gal4/dsRed:14xUAS:YapS87A embryos were pooled for one sample. Three wild type and three vsx2:Gal4/dsRed:14xUAS:YapS87A pools were analyzed for RNA.
2015-08-06 | E-GEOD-71681 | biostudies-arrayexpress
Project description:The Hippo pathway plays a crucial in organ size control during development and tissue homeostasis in adult life. To examine a role for Hippo signaling in the intestinal epithelium, we analyzed gene expression patterns in the mouse intestinal epithelilum transfected with siRNAs or expression plasmids for shRNAs targeting the Hippo pathway effectors, YAP and TAZ. We performed two independent series of experiments (siGFP (n=3) vs siYAP/siTAZ (n=3), and shLacZ (n=1) vs shYAP/shTAZ (n=1)). Control siRNA (siGFP), YAP/TAZ siRNAs, or expression plasmids for control shRNA (shLacZ) or YAP/TAZ shRNAs were introduced into the mouse intestinal epithelium by the newly-developed in vivo transfection method. Four days after transfection, intestinal epithelial cells were isolated from the tissues and total RNA was extracted.
2014-07-18 | E-GEOD-45155 | biostudies-arrayexpress