A general mechanism for transcription regulation by Oct1 and Oct4 in response to genotoxic and oxidative stress
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE14283 | GEO | 2009/01/22
SECONDARY ACCESSION(S): PRJNA111253
REPOSITORIES: GEO
Similar Datasets
Project description:We identify inducible binding of the transcription factor Oct1 to numerous targets following exposure to hydrogen peroxide. Oct1 bound ChIP fragments were sequenced in the presence and absence of H2O2 exposure using HeLa cells. Both 26 and 36bp reads were generated. Each processed file contains a list of genomic regions (NCBI 36.1, H_sapiens_Mar_2006, hg18) enriched for Oct1 binding. These files were generated by running the EnrichedRegionMaker on ScanSeqs window scored data, see http://useq.sourceforge.net/ . Adjacent and overlapping windows with a q-value FDR of 0.0001 were joined into larger enriched regions. The best scoring window's scores are used to represent the enriched region.
2009-01-22 | E-GEOD-14283 | biostudies-arrayexpress
Project description:Gene expression changes in response to aging, hyperoxia, hydrogen peroxide, ionizing radiation, and heat stress were compared using microarrays. While aging shared features with each stress, aging was more similar to the stresses most associated with oxidative stress (hydrogen peroxide, hyperoxia, ionizing radiation) than to heat stress. Aging is associated with down-regulation of numerous mitochondrial genes, including electron-transport-chain (ETC) genes and mitochondrial metabolism genes, and a sub-set of these changes was also observed upon hydrogen peroxide stress and ionizing radiation stress. Aging shared the largest number of gene expression changes with hyperoxia. The extensive down-regulation of mitochondrial and ETC genes during aging is consistent with an aging-associated failure in mitochondrial maintenance, which may underlie the oxidative stress-like and proteotoxic stress-like responses observed during aging.
2012-11-19 | GSE42255 | GEO
Project description:Gene expression changes in response to aging, hyperoxia, hydrogen peroxide, ionizing radiation, and heat stress were compared using microarrays. While aging shared features with each stress, aging was more similar to the stresses most associated with oxidative stress (hydrogen peroxide, hyperoxia, ionizing radiation) than to heat stress. Aging is associated with down-regulation of numerous mitochondrial genes, including electron-transport-chain (ETC) genes and mitochondrial metabolism genes, and a sub-set of these changes was also observed upon hydrogen peroxide stress and ionizing radiation stress. Aging shared the largest number of gene expression changes with hyperoxia. The extensive down-regulation of mitochondrial and ETC genes during aging is consistent with an aging-associated failure in mitochondrial maintenance, which may underlie the oxidative stress-like and proteotoxic stress-like responses observed during aging. Thirty five sample of RNA including Stress Controls (4 replicates), Heat Stress (3 replicates), Ionizing Radiation (4 replicates), Sugar (4 replicates), Hydrogen Peroxide (4 replicates), Young Controls (6 replicates) , Hyperoxia (6 replicates) and Old (4 replicates) adult Drosophila were analysed by Affymetrix microarrays. Stress Controls were used as controls for Heat Stress, Ionizing Radiation, Sugar and Hydrogen Peroxide samples. Young Controls were used as controls for Hyperoxia and Old samples. All flies were male progeny of a cross between Oregon-R wildtype and transgenic strain w[1118];P{w+ rtTA}(3)[E2]/ TM3. Flies lacking the balancer but bearing the transgene were used.
2012-11-19 | E-GEOD-42255 | biostudies-arrayexpress
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. Oct1 is an AR interacting partner and regulates the transcriptional activity of AR. In order to investigate the Oct1 function in prostate cancer cells, we performed gene expression in AR-positive prostate cancer cell lines after siOct1 or pyrrole-imidazole (PI) polyamide targeting Oct1-binding treatment. We also treated cells with vehicle or androgen to analyze the effects of Oct1 on AR function. Observation of androgen dependent gene expression changes after treatment with siOct1 or polyamide targeting Oct1 with microarray.
2016-04-01 | E-GEOD-77650 | biostudies-arrayexpress
Project description:3D spheroids of primary human hepatocytes (3D PHH) keep a differentiated phenotype with retained metabolic function and proteome fingerprint for weeks in culture. As a result, 3D PHH are gaining ground as a model for mechanistic studies on liver homeostasis and in vitro to in vivo (IVIV)predictions in drug discovery. However, the function of drug-transporting proteins has not yet been studied in the 3D PHH. Here we used the organic cation transporter 1 (OCT1/SLC22A1) as a model to explore both transporter kinetics and long-term regulation of transporter activity via different pathways. The 3D PHH were cultured for one week and then used for short- and long-term studies. The OCT1 transporter kinetics was assessed using the fluorescent model substrate 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP+) and known OCT1 inhibitors in individual 3D PHH. For long-term studies, the 3D PHH were exposed to xenobiotics for seven days, after which protein expression and OCT1 function were assessed. Global proteomics analysis was used to track prototypical changes of other regulated proteins. ASP+ kinetics indicated a fully functional OCT1 transporter with a Km value of 14.14±3.97 using three donors. Established OCT1 inhibitors reduced the uptake of ASP+ in the 3D PHH spheroids, resulting in 40-60% of the maximal uptake rate of ASP+. The long-term exposure studies showed that OCT1 is relatively stable to the activation of a broad range of pathways known to regulate ADME proteins. Importantly, while expression levels of other ADME proteins, such as CYP3A4 and MDR1 were regulated as expected, OCT1 levels remained stable. In conclusion, our results show for the first time that 3D PHH spheroids express fully active OCT1 and that transporter kinetics can be studied in 3D PHH. We also confirm that OCT1 remains stable and functional during activation of various pathways that alter the expression and function of other ADME proteins.
2024-08-10 | PXD045733 | Pride
Project description:Prostate cancer is the most common cancer in men and AR downstream signalings promote prostate cancer cell proliferation. Oct1 is an AR interacting partner and regulates the transcriptional activity of AR. In order to investigate the Oct1 function in prostate cancer cells, we performed gene expression in AR-positive prostate cancer cell lines after siOct1 or pyrrole-imidazole (PI) polyamide targeting Oct1-binding treatment. We also treated cells with vehicle or androgen to analyze the effects of Oct1 on AR function.
2016-04-01 | GSE77650 | GEO
Project description:The idea was to examine the role of OxyR in control of the oxidative stress response of B. fragilis when exposed to either atmospheric oxygen, 5% oxygen atmosphere, or hydrogen peroxide Keywords: stress response
2007-12-30 | GSE4583 | GEO
Project description:Embryonic stem cells (ESCs) co-express Oct4/POU5F1 and an Oct4 paralog known Oct1/POU2F1. To study the role of Oct1 in embryonic stem cell transcriptional control and pluripotency, we constructed germline and inducible-conditional Oct1 deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal, growth rates and metabolic signatures. However loss of Oct1 results in defective lineage specification. ESCs lacking Oct1 fail to form beating cardiomyocytes in culture, generate neurons poorly, form smaller, less differentiated teratomas, and are incapable of generating chimeric mice. Upon RA-mediated neuronal differentiation, Oct1 deficient cells fail to properly induce developmentally poised genes. Simultaneously, genes for alternative developmental pathways, most notably for the development of extra-embryonic tissues, are inappropriately expressed. ChIP experiments show that Oct1 does not occupy pluripotency genes or differentially expressed developmental targets in ESCs. Additionally, Oct1 occupies developmental targets as cells differentiate and Oct4 is lost. These results are consistent with a role for Oct1 in promoting the expression of lineage-specific genes in differentiating cells while simultaneously repressing genes specific for alternative lineages.
2017-05-24 | GSE85061 | GEO
Project description:Embryonic stem cells (ESCs) co-express Oct4/POU5F1 and an Oct4 paralog known Oct1/POU2F1. To study the role of Oct1 in embryonic stem cell transcriptional control and pluripotency, we constructed germline and inducible-conditional Oct1 deficient ESC lines. ESCs lacking Oct1 show normal appearance, self-renewal, growth rates and metabolic signatures. However loss of Oct1 results in defective lineage specification. ESCs lacking Oct1 fail to form beating cardiomyocytes in culture, generate neurons poorly, form smaller, less differentiated teratomas, and are incapable of generating chimeric mice. Upon RA-mediated neuronal differentiation, Oct1 deficient cells fail to properly induce developmentally poised genes. Simultaneously, genes for alternative developmental pathways, most notably for the development of extra-embryonic tissues, are inappropriately expressed. ChIP experiments show that Oct1 does not occupy pluripotency genes or differentially expressed developmental targets in ESCs. Additionally, Oct1 occupies developmental targets as cells differentiate and Oct4 is lost. These results are consistent with a role for Oct1 in promoting the expression of lineage-specific genes in differentiating cells while simultaneously repressing genes specific for alternative lineages.
2017-05-24 | GSE85062 | GEO
Project description:The tumor suppressor BRCA1 regulates DNA damage responses and multiple other processes. Among these, BRCA1 heterodimerizes with BARD1 to ubiquitylate targets via its N-terminal RING domain. Here we show that BRCA1 promotes oxidative metabolism via degradation of Oct1, a transcription factor with pro-glycolytic/tumorigenic effects. BRCA1 E3 ubiquitin ligase mutation skews cells towards a glycolytic metabolic profile while elevating Oct1 protein. CRISPR-mediated Oct1 deletion reverts the glycolytic phenotype. RNAseq confirms the deregulation of metabolic genes. BRCA1 mediates direct Oct1 ubiquitylation and degradation, and mutation of two ubiquitylated Oct1 lysines insulates the protein against BRCA1-mediated destabilization. Oct1 deletion in MCF-7 breast cancer cells does not perturb growth in standard culture, but inhibits growth in soft agar and xenografts. Oct1 protein levels correlate positively with tumor aggressiveness, and inversely with BRCA1, in primary breast cancer samples. These results identify BRCA1 as an Oct1 ubiquitin ligase that catalyzes Oct1 degradation to promote oxidative metabolism.
2017-11-30 | GSE98831 | GEO