Similar Datasets
Project description:In this study, we performed mRNA sequencing on IMR90 and A549 cells in order to understand the differences in gene expression patterns and alternative splicing patterns between the two cell lines.
2021-05-23 | GSE146164 | GEO
Project description:Here, we set out to understand if and how splicing kinetics are coordinated beyond individual intron removal and if this potential coordination could regulate alternative splicing outcomes. By measuring rates of transcription and splicing genome-wide, we found that the rate of splicing is coordinated across introns within individual genes. Furthermore, we found that elongation rates and splicing rates are coordinated within TADs, as are alternative splicing changes that result from cell type differences, differentiation programs, and alterations in splicing factor levels. Overall, our work establishes that the kinetics of transcription and splicing are coordinated within the spatial organization of the genome, which could be a control point for alternative splicing regulation that can modulate the function of a cell.
2021-05-23 | GSE146161 | GEO
Project description:Transcription and splicing kinetics are coordinated within both genes and higher-order chromatin domains
| PRJNA609986 | ENA
Project description:Transcription and splicing kinetics are coordinated within both genes and higher-order chromatin domains [dataset1]
| PRJNA609632 | ENA
Project description:Transcription and splicing kinetics are coordinated within both genes and higher-order chromatin domains [dataset2]
| PRJNA609643 | ENA
Project description:The detailed principles of the hierarchical folding of eukaryotic chromosomes have been revealed during the last two decades. Along with structures composing three-dimensional (3D) genome organization (chromatin compartments, topologically associating domains, chromatin loops, etc.), the molecular mechanisms that are involved in their establishment and maintenance have been characterized. Generally, protein-protein and protein-DNA interactions underlie the spatial genome organization in eukaryotes. However, it is becoming increasingly evident that weak interactions, which exist in biological systems, also contribute to the 3D genome. Here, we provide a snapshot of our current understanding of the role of the weak interactions in the establishment and maintenance of the 3D genome organization. We discuss how weak biological forces, such as entropic forces operating in crowded solutions, electrostatic interactions of the biomolecules, liquid-liquid phase separation, DNA supercoiling, and RNA environment participate in chromosome segregation into structural and functional units and drive intranuclear functional compartmentalization.
| S-EPMC7229822 | biostudies-literature
Project description:Packing of about two meters of the human genome DNA into chromatin occupying a several micron-sized cell nucleus requires a high degree of compaction in a manner that allows the information encoded on DNA to remain easily accessible. This packing is mediated by repeated coiling of DNA double helix around histones to form nucleosome arrays that are further folded into higher-order structures. Relatively straight DNA linkers separate the nucleosomes and the spacing between consecutive nucleosome varies between different cells and between different chromosomal loci. In a recent work ( 1) our group used a biochemically defined in vitro reconstituted system to explore how do various DNA linkers mediate nucleosome array packing into higher-order chromatin structures. For long nucleosome linkers (about 60 bp) we observed a more open chromatin structure and no effect of small linker length alterations (±2-4 bp) on chromatin folding. In striking contrast, for shorter linkers (20-32 bp) we found more compact packing with strong periodical dependence upon the linker DNA lengths. Our data together with high-resolution nucleosome position mapping provide evidence for the natural nucleosome repeats to support a chromatin architecture that, by default, restricts spontaneous folding of nucleosome arrays into compact chromatin fibers. We suggest that incomplete folding of the nucleosome arrays may promote global inter-array interactions that lead to chromatin condensation in metaphase chromosomes and heterochromatin.
| S-EPMC3515531 | biostudies-literature
Project description:NUT midline carcinoma (NMC), a subtype of squamous cell cancer, is one of the most aggressive human solid malignancies known. NMC is driven by the creation of a translocation oncoprotein, BRD4-NUT, which blocks differentiation and drives growth of NMC cells. BRD4-NUT forms distinctive nuclear foci in patient tumors, which we found correlate with ∼100 unprecedented, hyperacetylated expanses of chromatin that reach up to 2 Mb in size. These "megadomains" appear to be the result of aberrant, feed-forward loops of acetylation and binding of acetylated histones that drive transcription of underlying DNA in NMC patient cells and naïve cells induced to express BRD4-NUT. Megadomain locations are typically cell lineage-specific; however, the cMYC and TP63 regions are targeted in all NMCs tested and play functional roles in tumor growth. Megadomains appear to originate from select pre-existing enhancers that progressively broaden but are ultimately delimited by topologically associating domain (TAD) boundaries. Therefore, our findings establish a basis for understanding the powerful role played by large-scale chromatin organization in normal and aberrant lineage-specific gene transcription.
| S-EPMC4526735 | biostudies-literature
Project description:The structure of the higher-order chromatin fiber has not been defined in detail. We have used a novel approach based on sucrose gradient centrifugation to compare the conformation of centromeric satellite DNA-containing higher-order chromatin fibers with bulk chromatin fibers obtained from the same mouse fibroblast cells. Our data show that chromatin fibers derived from the centromeric domain of a chromosome exist in a more condensed structure than bulk chromatin whereas pericentromeric chromatin fibers have an intermediate conformation. From the standpoint of current models, our data are interpreted to suggest that satellite chromatin adopts a regular helical conformation compatible with the canonical 30-nm chromatin fiber whereas bulk chromatin fibers appear less regularly folded and are perhaps intermittently interrupted by deformations. This distinctive conformation of the higher-order chromatin fiber in the centromeric domain of the mammalian chromosome could play a role in the formation of heterochromatin and in the determination of centromere identity.
| S-EPMC59820 | biostudies-literature
Project description:We statistically characterize the population spiking activity obtained from simultaneous recordings of neurons across all layers of a cortical microcolumn. Three types of models are compared: an Ising model which captures pairwise correlations between units, a Restricted Boltzmann Machine (RBM) which allows for modeling of higher-order correlations, and a semi-Restricted Boltzmann Machine which is a combination of Ising and RBM models. Model parameters were estimated in a fast and efficient manner using minimum probability flow, and log likelihoods were compared using annealed importance sampling. The higher-order models reveal localized activity patterns which reflect the laminar organization of neurons within a cortical column. The higher-order models also outperformed the Ising model in log-likelihood: On populations of 20 cells, the RBM had 10% higher log-likelihood (relative to an independent model) than a pairwise model, increasing to 45% gain in a larger network with 100 spatiotemporal elements, consisting of 10 neurons over 10 time steps. We further removed the need to model stimulus-induced correlations by incorporating a peri-stimulus time histogram term, in which case the higher order models continued to perform best. These results demonstrate the importance of higher-order interactions to describe the structure of correlated activity in cortical networks. Boltzmann Machines with hidden units provide a succinct and effective way to capture these dependencies without increasing the difficulty of model estimation and evaluation.
| S-EPMC4081002 | biostudies-literature