Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA242680 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Enhancer elements interact with target genes at a distance to modulate their expression, but the molecular details of enhancer-promoter interaction are incompletely understood. G-quadruplex DNA secondary structures (G4s) have recently been shown to co-occur with 3D chromatin interactions, however, the functional importance of G4s within enhancers remains unclear. Results: In this study we identify novel G4 structures within two locus control regions at the human - and - globin loci. We find that mutating G4 motifs by genome editing prevents their folding into G4 structures in cells and disrupts 3D enhancer-promoter interactions and target gene expression in a manner comparable to whole enhancer deletion. Furthermore, restoration of G4 structure formation using a dissimilar G4-forming primary sequence recovers specific enhancer-gene interactions and gene expression. Through proteomic, biophysical, and genomic profiling, we find that enhancer G4s are tightly linked to the maintenance of an active chromatin state and RNA polymerase II recruitment to regulate target gene expression.
2025-06-05 | PXD063882 | Pride
Project description:Enhancer elements interact with target genes at a distance to modulate their expression, but the molecular details of enhancer-promoter interaction are incompletely understood. G-quadruplex DNA secondary structures (G4s) have recently been shown to co-occur with 3D chromatin interactions, however, the functional importance of G4s within enhancers remains unclear. Results: In this study we identify novel G4 structures within two locus control regions at the human α- and β- globin loci. We find that mutating G4 motifs by genome editing prevents their folding into G4 structures in cells and disrupts 3D enhancer-promoter interactions and target gene expression in a manner comparable to whole enhancer deletion. Furthermore, restoration of G4 structure formation using a dissimilar G4-forming primary sequence recovers specific enhancer-gene interactions and gene expression. Through proteomic, biophysical, and genomic profiling, we find that enhancer G4s are tightly linked to the maintenance of an active chromatin state and RNA polymerase II recruitment to regulate target gene expression.
2025-05-13 | GSE267666 | GEO
Project description:G4 are noncanonical secondary structures consist in stacked tetrads of Hoogsteen hydrogen-bonded guanines bases. An essential feature of G-quadruplexes is their intrinsic polymorphic nature. Indeed, depending on the length and the composition of the sequence, as well as the environmental conditions (including the nature and concentration of metal cations, and local molecular crowding), a G-quadruplex-forming sequence can adopt different topologies in which the strands are in parallel or antiparallel conformations, with the co-existence of different types of loops (lateral, diagonal or propeller) with variable lengths. The impact of G4 on cellular metabolism is associated with protein or enzymatic factors that promote, inhibits or resolve these structures. Thus, the major impact of G4 on the human cell metabolism is associated with genetic defects affecting proteins that counteract their formation. Although a large number of proteins able to bind and/or "to resolve" G-quadruplex structures have been identified in vitro, less is known about their mode of interaction with G-quadruplex, their specificity versus the topology and finally their specificity for G4 structures relatively to G-rich single-stranded sequences. In this study we aimed to identify and characterize human proteins interacting with locked G4 structures.
2021-07-16 | PXD021003 | Pride
Project description:Expression data from transfection of two different antisense oligonucleotides in HuH7 cells
| PRJNA360414 | ENA
Project description:Expression data from transfection of 14 different antisense oligonucleotides in HuH7 cells
| PRJNA360415 | ENA
Project description:In this study we discover proteins that bind to G4 quadruplex DNA structure. We use modified c-myc quadruplex as a bait, and compare it to the control bait - T15 oligo. We use spectral counts and G-test to determine significant binders. T15 and G4 datafiles are uploaded
2016-07-07 | PXD003501 | Pride
Project description:The effect of bisquinolinium compounds PhenDC3 and 360A genome wide gene expression changes modulated via promoter based G-quadruplex (G4) motifs. The total RNA was extracted after treating HeLa S3 cells with 10 µM of no molecule (DMSO), 8979A (control molecule), PhenDC3 (G4 specific molecule) or 360A (G4 specific molecule) for 48 hrs in triplicate.
2012-05-29 | E-GEOD-32170 | biostudies-arrayexpress
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:RNA extracted at 240min. Samples are rRNA depleted. Expression measurement of Homo sapiens genes.
2019-07-31 | GSE114179 | GEO
Project description:Telomere erosion causes cell mortality, suggesting that longer telomeres allow greater number of cell division. In telomerase-positive human cancer cells, however, telomeres are often kept shorter than the surrounding normal tissues. Recently, we have shown that telomere elongation in cancer cells represses innate immune genes and promotes their differentiation in vivo. This implies that short telomeres contribute to cancer malignancy, but it is unclear how such genetic repression is caused by long telomeres. Here we report that telomeric repeat-containing RNA (TERRA) induces genome-wide alteration of gene expression in telomere-elongated cancer cells in vivo. Using three different cell lines, we found that G4 forming oligonucleotide repressed innate immune genes in vivo 3D culture conditions. Most of the suppressed genes belonged to innate immune system categories and were upregulated in various cancers. We propose that TERRA G4 counteracts cancer malignancy through suppression of innate immune genes. Six samples are G4 oligo-transfected cells (PC-3/(uuaggg)^4, PC-3/AS1411, HBC4/(uuaggg)^4, HBC4/AS1411, MKN74/(uuaggg)^4 and MKN74/AS1411), and the other six samples are control oligo-transfected cells.
2015-02-05 | E-GEOD-56239 | biostudies-arrayexpress