PhIP-Seq LLD
Ontology highlight
ABSTRACT:
PROVIDER: EGAS00001006999 | EGA |
REPOSITORIES: EGA
Similar Datasets
Project description:PHF6 is a transcriptional regulator mutated in 3-5% of acute myeloid leukemia. To understand how PHF6 and its functional partner PHIP interact with each other on chromatin, we performed ChIP-Seq for PHF6 (in the presence and absence of PHIP), for PHF6R274Q mutant, and for PHIP. We observd that PHF6 and PHIP peaks overlap on chromatin, and PHF6 requires PHIP for its chromatin occupancy. ATAC-Seq and H3K27ac ChIP-Seq showed that PHF6 and PHIP occupy open and active regions of the genome.
2024-11-15 | GSE281629 | GEO
Project description:PHF6 is a transcriptional regulator mutated in 3-5% of acute myeloid leukemia. To understand how PHF6 and its functional partner PHIP interact with each other on chromatin, we performed ChIP-Seq for PHF6 (in the presence and absence of PHIP), for PHF6R274Q mutant, and for PHIP. We observd that PHF6 and PHIP peaks overlap on chromatin, and PHF6 requires PHIP for its chromatin occupancy. ATAC-Seq and H3K27ac ChIP-Seq showed that PHF6 and PHIP occupy open and active regions of the genome.
2024-11-15 | GSE281627 | GEO
Project description:PHF6 is a transcriptional regulator mutated in 3-5% of acute myeloid leukemia. To understand how PHF6 and its functional partner PHIP interact with each other on chromatin, we performed ChIP-Seq for PHF6 (in the presence and absence of PHIP), for PHF6R274Q mutant, and for PHIP. We observd that PHF6 and PHIP peaks overlap on chromatin, and PHF6 requires PHIP for its chromatin occupancy. ATAC-Seq and H3K27ac ChIP-Seq showed that PHF6 and PHIP occupy open and active regions of the genome.
2024-11-15 | GSE281628 | GEO
Project description:PHF6 is a transcriptional regulator mutated in 3-5% of acute myeloid leukemia. To understand the effect of loss and clinical mutation of PHF6 on the transcriptome of myeloid cells, we generated multiple wildtype and PHF6 knockout clones, as well as clones expressing the most common clinical mutant of the protein-PHF6R274Q. We observed that both single and double knockouts and mutation of PHF6 shifted the cells towards stemness and away from differentiation. Additionally we identified PHIP as a possible functional partner for PHF6. To investigate their common biological function, we generated multiple single knockout clones of PHIP as well as double knockout clones of PHIP and PHF6, and observed that, similar to single knockout of PHF6, PHIP knockout and double knockout also shifted cells towards stemness and away from differentiation. Collectively, our experiments show that PHF6 and PHIP, separately identified as being mutated in AML, exert similar downstream effects on the AML transcriptome.
2024-11-15 | GSE281475 | GEO
Project description:The PHIP chromatin reader protein is mutated in Chung-Jansen syndrome, a neurodevelopmental disorder with autism like symptoms. Here we have characterized the chromatin binding properties of PHIP using a variety of in vitro and in vivo methods.
2021-11-22 | GSE189235 | GEO
Project description:Although various mechanisms have been inferred for combinatorial actions of multiple carcinogens, these mechanisms have not been well demonstrated in experimental carcinogenesis models. We evaluated mammary carcinogenesis initiated by combined exposure to various doses of radiation and chemical carcinogens. Female rats at 7 weeks of age were M-NM-3-irradiated (0.2M-bM-^@M-^S2 Gy) and/or exposed to 1-methyl-1-nitrosourea (20 or 40 mg/kg, single intraperitoneal injection) or 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (40 mg/kg/day by gavage for 10 days) and were observed until 50 weeks of age. The incidence of mammary carcinoma increased steadily as a function of radiation dose in the absence of chemicals; mathematical analysis supported an additive increase when radiation was combined with a chemical carcinogen, irrespective of the chemical species and its dose. Hras mutations were characteristic of carcinomas that developed after chemical carcinogen treatments and were overrepresented in carcinomas induced by the combination of radiation and MNU (but not PhIP), indicating an interaction of radiation and MNU at the level of initiation. The expression profiles of seven classifier genes, previously shown to distinguish two classes of rat mammary carcinomas, categorized almost all examined carcinomas that developed after individual or combined treatments with radiation (1 Gy) and chemicals as belonging to a single class; more comprehensive screening using microarrays and a separate test sample set failed to identify differences in gene expression profiles among these carcinomas. These results suggest that a complex, multilevel interaction underlies the combinatorial action of radiation and chemical carcinogens in the experimental model. Mammary cancers were from untreated rats (n = 3) and rats treated with radiation (1 Gy; n = 4), MNU (40 mg/kg; H-rasM-bM-^@M-^Smutated cancers, n = 5; H-rasM-bM-^@M-^Snonmutated cancers, n = 4), PhIP (H-rasM-bM-^@M-^Smutated, n = 1; H-rasM-bM-^@M-^Snonmutated, n = 3), radiation 1 Gy plus MNU (40 mg/kg; H-rasM-bM-^@M-^Smutated, n = 5; H-rasM-bM-^@M-^Snonmutated, n = 4) and radiation 1 Gy plus PhIP (H-rasM-bM-^@M-^Snonmutated , n = 4). Normal mammary tissues were from untreated rats (n = 3).
2013-08-29 | E-GEOD-44786 | biostudies-arrayexpress
Project description:The gene expression profling between Control and 300 mg/kg PhIP treatment in ventral prostate lobe of male F344 rats
2018-03-15 | GSE95214 | GEO
Project description:SWI/SNF chromatin remodeling complexes are perturbed in 20% of all cancers and several developmental disorders, yet the mechanisms by which these mutations dysregulate transcription and drive disease are poorly understood. To both elucidate these mechanisms and identify vulnerabilities caused by these mutations, we leveraged genome-wide CRISPR-Cas9 screening in hundreds of cancer cell lines and identified the chromatin reader protein PHIP as a specific dependency in cancers with broadly disrupted SWI/SNF function. Mechanistically, we reveal that PHIP cooperates with SWI/SNF to facilitate transcriptional activation by ubiquitinating and suppressing subunits of the repressive Nucleosome Remodeling and Deacetylase (NuRD) complex. We demonstrate that loss of SWI/SNF results in NuRD complexes accumulating at promoters where they would otherwise cause widespread transcriptional silencing if not antagonized by PHIP. Collectively, we identify PHIP as a regulator of the interplay between distinct chromatin regulators that function in development and disease and as a targetable vulnerability in cancers with broad SWI/SNF inactivation.
2026-02-09 | GSE299672 | GEO
Project description:SWI/SNF chromatin remodeling complexes are perturbed in 20% of all cancers and several developmental disorders, yet the mechanisms by which these mutations dysregulate transcription and drive disease are poorly understood. To both elucidate these mechanisms and identify vulnerabilities caused by these mutations, we leveraged genome-wide CRISPR-Cas9 screening in hundreds of cancer cell lines and identified the chromatin reader protein PHIP as a specific dependency in cancers with broadly disrupted SWI/SNF function. Mechanistically, we reveal that PHIP cooperates with SWI/SNF to facilitate transcriptional activation by ubiquitinating and suppressing subunits of the repressive Nucleosome Remodeling and Deacetylase (NuRD) complex. We demonstrate that loss of SWI/SNF results in NuRD complexes accumulating at promoters where they would otherwise cause widespread transcriptional silencing if not antagonized by PHIP. Collectively, we identify PHIP as a regulator of the interplay between distinct chromatin regulators that function in development and disease and as a targetable vulnerability in cancers with broad SWI/SNF inactivation.
2026-02-09 | GSE299562 | GEO
Project description:The estimation of acceptable exposure levels for genotoxicants is accomplished by defining thresholds from apical endpoints, or by modeling points of departure from data that are acquired from high dose experiments, followed by linear extrapolation of the response through zero. We recently proposed that low dose exposure-induced transcriptional changes that can be linked to mechanisms of pathogenesis could provide a more sensitive alternative for defining thresholds for biological responses. In the present study, we used gene expression profiling data to determine an empirical transcriptional dose response threshold for the food and tobacco smoke borne carcinogen, 2-amino-1-methyl-6-phenylimidazo[4,5]pyridine (PhIP) in human BEAS-2B bronchial epithelial cells exposed to concentrations of N-hydroxylated PhIP ranging from 1 x 10-6 to 5 x 10-10 M. The goal was to determine transcriptional dose response threshold (NOTEL) of human BEAS-2B bronchial epithelial cells exposed to the food and tobacco smoke borne carcinogen, 2-hydroxy-mino-1-methyl-6-phenylimidazo[4,5]pyridine (N-OH-PhIP). BEAS-2B cells at ~ 70% confluence were treated with doses of N-OH-PhIP that varied over five orders or magnitude. Triplicate cell cultures were exposed to either DMS (control) or nine different doses of N-OH-PhIP at concentrations ranging from 1 x 10-6 to 5 x 10-10 M.
2011-12-22 | E-GEOD-34635 | biostudies-arrayexpress