Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA295216 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR2320760.fastq.gz | Fastqsanger.gz | |||
| SRR2320762.fastq.gz | Fastqsanger.gz | |||
| SRR2320756.fastq.gz | Fastqsanger.gz | |||
| SRR2320758.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 4 of 4 |
Similar Datasets
Project description:WD repeat domain 5 (WDR5) plays an important role in various biological functions through the epigenetic regulation of gene transcription. However, the oncogenic effect of WDR5 in leukemia remains largely unknown. Here, we found WDR5 expression is increased in leukemia patients. High expression of WDR5 is associated with high risk leukemia; Patients with WDR5 and MLL1 high expression have poor complete remission rate. We further identified the global genomic binding of WDR5 in leukemic cells and found the genomic co-localization of WDR5 binding with H3K4me3 enrichment. Moreover, WDR5 knockdown by shRNA suppresses cell proliferation, induces apoptosis, inhibits the expression of WDR5 targets, and blocks the H3K4me3 enrichment on the promoter of its targets. We also observed the positive correlation of WDR5 expression with these targets in the cohort study of leukemia patients. Our data reveal that WDR5 may have oncogenic effect and WDR5-mediated H3K4 methylation plays an important role in leukemogenesis.
2016-12-30 | GSE72864 | GEO
Project description:Biochemical interactions between WD40 repeat domain protein 5 (WDR5) and its various cellular partners such as Mixed Lineage Leukemia (MLL) and c-MYC are essential for sustaining oncogenesis in a range of human cancers. Thus, small molecules targeting WDR5 represent an attractive strategy for anti-cancer interventions. However, currently available inhibitors designed to interfere with WDR5 binding to a specific partner (such as OICR-9429 that blocks WDR5-MLL interaction) show a promising but rather partial therapeutic effect, presumably due to incomplete blockade of WDR5 functionality and interactions with various partners. Here, we report the first-in-class, OICR-9429-based proteolysis targeting chimeras (PROTACs) of WDR5, including a prototypic compound MS33 and a further optimized MS67, that achieve specific and efficient depletion of WDR5 in cancer cells. Such an effect is not seen with OICR-9429 or MS33/67 analogs that are incapable of E3 ligand conjugation. Medicinal chemistry, structural and cellular characterizations demonstrate that MS33 and MS67 bind both WDR5 and an E3 ligand VHL tightly, with MS67 showing a unique cooperative binding, an event that subsequently induces degradation of WDR5 through a VHL- and proteasome-dependent mechanism. Global proteomics profiling shows a highly specific effect of MS67 on WDR5. Genomics analysis further demonstrates that, relative to non-degrading inhibitors, MS67 is far more potent in suppressing overall transcription of WDR5-regulated genes crucially involved in oncogenesis and in reducing global H3K4 methylation, an enzymatic product of MLL/WDR5 complex. Importantly, using a panel of human MLL-rearranged acute myeloid leukemia (MLL-r AML) and pancreatic ductal adenocarcinoma (PDAC) cells, we found that, relative to non-degrading inhibitor controls, MS67 displays a superior anti-growth effect. MS67 also demonstrates optimal PK/PD properties in vivo and treatment with MS67 significantly suppressed tumorigenesis of MLL-r AML in tumor xenografted animal models. Together, this study reports the first-in-class PROTACs of WDR5 and demonstrates its advantageous efficacies in the treatment of WDR5-dependent cancers.
2021-09-29 | GSE150552 | GEO
Project description:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Gene expression profiling of immortalized human mesenchymal stem cells with hTERT/E6/E7 transfected MSCs. hTERT may change gene expression in MSCs. Goal was to determine the gene expressions of immortalized MSCs.
2010-09-25 | GSE24338 | GEO
Project description:Kynureninase is a member of a large family of catalytically diverse but structurally homologous pyridoxal 5'-phosphate (PLP) dependent enzymes known as the aspartate aminotransferase superfamily or alpha-family. The Homo sapiens and other eukaryotic constitutive kynureninases preferentially catalyze the hydrolytic cleavage of 3-hydroxy-l-kynurenine to produce 3-hydroxyanthranilate and l-alanine, while l-kynurenine is the substrate of many prokaryotic inducible kynureninases. The human enzyme was cloned with an N-terminal hexahistidine tag, expressed, and purified from a bacterial expression system using Ni metal ion affinity chromatography. Kinetic characterization of the recombinant enzyme reveals classic Michaelis-Menten behavior, with a Km of 28.3 +/- 1.9 microM and a specific activity of 1.75 micromol min-1 mg-1 for 3-hydroxy-dl-kynurenine. Crystals of recombinant kynureninase that diffracted to 2.0 A were obtained, and the atomic structure of the PLP-bound holoenzyme was determined by molecular replacement using the Pseudomonas fluorescens kynureninase structure (PDB entry 1qz9) as the phasing model. A structural superposition with the P. fluorescens kynureninase revealed that these two structures resemble the "open" and "closed" conformations of aspartate aminotransferase. The comparison illustrates the dynamic nature of these proteins' small domains and reveals a role for Arg-434 similar to its role in other AAT alpha-family members. Docking of 3-hydroxy-l-kynurenine into the human kynureninase active site suggests that Asn-333 and His-102 are involved in substrate binding and molecular discrimination between inducible and constitutive kynureninase substrates.
| S-EPMC2531291 | biostudies-literature
Project description:Biochemical interactions between WD40 repeat domain protein 5 (WDR5) and its various cellular partners such as Mixed Lineage Leukemia (MLL) and c-MYC are essential for sustaining oncogenesis in a range of human cancers. Thus, small molecules targeting WDR5 represent an attractive strategy for anti-cancer interventions. However, currently available inhibitors designed to interfere with WDR5 binding to a specific partner (such as OICR-9429 that blocks WDR5-MLL interaction) show a promising but rather partial therapeutic effect, presumably due to incomplete blockade of WDR5 functionality and interactions with various partners. Here, we report the first-in-class, OICR-9429-based proteolysis targeting chimeras (PROTACs) of WDR5, including a prototypic compound MS33 and a further optimized MS67, that achieve specific and efficient depletion of WDR5 in cancer cells. Such an effect is not seen with OICR-9429 or MS33/67 analogs that are incapable of E3 ligand conjugation. Medicinal chemistry, structural and cellular characterizations demonstrate that MS33 and MS67 bind both WDR5 and an E3 ligand VHL tightly, with MS67 showing a unique cooperative binding, an event that subsequently induces degradation of WDR5 through a VHL- and proteasome-dependent mechanism. Global proteomics profiling shows a highly specific effect of MS67 on WDR5. Genomics analysis further demonstrates that, relative to non-degrading inhibitors, MS67 is far more potent in suppressing overall transcription of WDR5-regulated genes crucially involved in oncogenesis and in reducing global H3K4 methylation, an enzymatic product of MLL/WDR5 complex. Importantly, using a panel of human MLL-rearranged acute myeloid leukemia (MLL-r AML) and pancreatic ductal adenocarcinoma (PDAC) cells, we found that, relative to non-degrading inhibitor controls, MS67 displays a superior anti-growth effect. MS67 also demonstrates optimal PK/PD properties in vivo and treatment with MS67 significantly suppressed tumorigenesis of MLL-r AML in tumor xenografted animal models. Together, this study reports the first-in-class PROTACs of WDR5 and demonstrates its advantageous efficacies in the treatment of WDR5-dependent cancers.
2021-09-29 | GSE150554 | GEO
Project description:As the evolution of miRNA genes has been found to be one of the important factors in formation of the modern type of man, we performed a comparative analysis of the evolution of miRNA genes in two archaic hominines, Homo sapiens neanderthalensis and Homo sapiens denisova, and elucidated the expression of their target mRNAs in bain.A comparative analysis of the genomes of primates, including species in the genus Homo, identified a group of miRNA genes having fixed substitutions with important implications for the evolution of Homo sapiens neanderthalensis and Homo sapiens denisova. The mRNAs targeted by miRNAs with mutations specific for Homo sapiens denisova exhibited enhanced expression during postnatal brain development in modern humans. By contrast, the expression of mRNAs targeted by miRNAs bearing variations specific for Homo sapiens neanderthalensis was shown to be enhanced in prenatal brain development.Our results highlight the importance of changes in miRNA gene sequences in the course of Homo sapiens denisova and Homo sapiens neanderthalensis evolution. The genetic alterations of miRNAs regulating the spatiotemporal expression of multiple genes in the prenatal and postnatal brain may contribute to the progressive evolution of brain function, which is consistent with the observations of fine technical and typological properties of tools and decorative items reported from archaeological Denisovan sites. The data also suggest that differential spatial-temporal regulation of gene products promoted by the subspecies-specific mutations in the miRNA genes might have occurred in the brains of Homo sapiens denisova and Homo sapiens neanderthalensis, potentially contributing to the cultural differences between these two archaic hominines.
| S-EPMC4686780 | biostudies-literature
Project description:PurposeWe investigated the evidence of recent positive selection in the human phototransduction system at single nucleotide polymorphism (SNP) and gene level.MethodsSNP genotyping data from the International HapMap Project for European, Eastern Asian, and African populations was used to discover differences in haplotype length and allele frequency between these populations. Numeric selection metrics were computed for each SNP and aggregated into gene-level metrics to measure evidence of recent positive selection. The level of recent positive selection in phototransduction genes was evaluated and compared to a set of genes shown previously to be under recent selection, and a set of highly conserved genes as positive and negative controls, respectively.ResultsSix of 20 phototransduction genes evaluated had gene-level selection metrics above the 90th percentile: RGS9, GNB1, RHO, PDE6G, GNAT1, and SLC24A1. The selection signal across these genes was found to be of similar magnitude to the positive control genes and much greater than the negative control genes.ConclusionsThere is evidence for selective pressure in the genes involved in retinal phototransduction, and traces of this selective pressure can be demonstrated using SNP-level and gene-level metrics of allelic variation. We hypothesize that the selective pressure on these genes was related to their role in low light vision and retinal adaptation to ambient light changes. Uncovering the underlying genetics of evolutionary adaptations in phototransduction not only allows greater understanding of vision and visual diseases, but also the development of patient-specific diagnostic and intervention strategies.
| S-EPMC3743458 | biostudies-literature
Project description:Transcriptional profiling of human mesenchymal stem cells comparing normoxic MSCs cells with hypoxic MSCs cells. Hypoxia may inhibit senescence of MSCs during expansion. Goal was to determine the effects of hypoxia on global MSCs gene expression.
2011-02-19 | GSE20463 | GEO
Project description:Cortical thickness has been investigated since the beginning of the 20th century, but we do not know how similar the cortical thickness profiles among humans are. In this study, the local similarity of cortical thickness profiles was investigated using sliding window methods. Here, we show that approximately 5% of the cortical thickness profiles are similarly expressed among humans while 45% of the cortical thickness profiles show a high level of heterogeneity. Therefore, heterogeneity is the rule, not the exception. Cortical thickness profiles of somatosensory homunculi and the anterior insula are consistent among humans, while the cortical thickness profiles of the motor homunculus are more variable. Cortical thickness profiles of homunculi that code for muscle position and skin stimulation are highly similar among humans despite large differences in sex, education, and age. This finding suggests that the structure of these cortices remains well preserved over a lifetime. Our observations possibly relativize opinions on cortical plasticity.
| S-EPMC5738339 | biostudies-literature