Project description:Embryonic stem (ES) cells express pluripotency-associated genes and repress differentiation-inducible genes. The activities of these genes are coordinately reversed during differentiation. The changes in the transcriptome upon conditional KAP1 knockout in ES cells overlapped with the changes during embryoid body formation. KAP1 repressed differentiation-inducible genes and derepressed pluripotency-associated genes in ES cells. KAP1 formed complexes with polycomb repressive complexes 1 (PRC1) through an interaction that was mediated by the KAP1 coiled-coil region. KAP1 and PRC1 bound cooperatively at the promoters of differentiation-inducible genes and repressed their transcription. In contrast, KAP1 bound the transcribed and flanking sequences of pluripotency-associated genes, did not enhance PRC1 binding, and derepressed their transcription. KAP1 had opposite effects on differentiation-inducible and pluripotency-associated gene transcription both in ES cells and in differentiating embryoid bodies. The region of KAP1 that mediated the interaction with PRC1 was required for KAP1 enhancement of PRC1 binding and for KAP1 repression of transcription at differentiation-inducible promoters. This region of KAP1 was not required for KAP1 suppression of PRC1 binding or for KAP1 derepression of transcription at pluripotency-associated promoters. The opposite effects of KAP1 on transcription of differentiation-inducible versus pluripotency-associated genes contributed to the reciprocal changes in their transcription during differentiation. Analysis of the regions occupied by KAP1(TRIM28/TIF1beta) and by Ring1b(Rnf2) in mouse embryonic stem cells before and after conditional KAP fl/fl and Ring1b fl/fl knockout

2014-07-29 | E-GEOD-56628 | biostudies-arrayexpress

E-MTAB-3503

Project description:Gene expression profiles of Rif1 inducible knock-out embryonic stem cells

2015-04-15 | E-MTAB-3503 | ExpressionAtlas

Clinical Evaluation - A Phase IIA Proof of Concept Study of Regorafenib (Bayer 73-4506) in Biopsy-amenable Asian Colorectal Cancer Patients

Project description:1. Primary Endpoints * Biomarker data suggestive of regorafenib-mediated inhibition of the RAS-RAF- MEK-ERK signal transduction pathway,of various tyrosine kinase receptors and/or of angiogenesis. * Evaluation of potential relationships between biomarker data and clinical activity. * Evaluation of a novel biomarker technology (Prometheus COPIA platform) 2. Secondary Endpoints * Biomarker data suggestive of regorafenib-mediated effects on circulating rare cells. * Comparison of tumor genetic profiles obtained using DNA isolated from plasma, tumor biopsies and circulating tumor cells. * Patient safety data * Pharmacokinetics of regorafenib * Changes in tumor metabolic activity as measured by PET CT scan (optional)

| 2094187 | ecrin-mdr-crc

A chemical-induced reversible gene knockout system for studying gene function in situ [AMP-seq]

Project description:We developed a conditional conversion allele system termed CoCo. Gene knockout is achieved through Cre-mediated transcription termination, whereas gene restoration is achieved by Flp-mediated deletion of termination signal. To tightly control the temporal expression of the recombinases, Tet-On inducible system is used to drive the expression of Cre recombinase and tamoxifen-inducible FlpO-ER fusion and therefore a dual drug-inducible conditional conversion system (DDCoCo) is developed. This system provides an efficient, rapid and flexible gene switch for studying gene function.

2021-11-13 | GSE188594 | GEO

A chemical-induced reversible gene knockout system for studying gene function in situ [RNA-seq]

2021-11-13 | GSE188384 | GEO

Deciphering functions of VHL in Clear Cell Renal Cell Carcinoma

Project description:VHL is the most frequently mutated gene in ccRCC.It functions via the oxygen-dependent ubiquitin-mediated degradation of hypoxia-inducible factor (HIF). The stabilization and hyperactivation of HIF1 play essential roles in tumorigenesis. This is a TMT based proteomics experiment aimed to investigate the functions of VHL in ccRCC systematically.

2023-01-05 | PXD012665 | Pride

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