Ontology highlight
ABSTRACT:
PROVIDER: PRJNA984408 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:We investigate the spectrum of SVs and three-dimensional (3D) chromatin architecture in human pancreatic ductal epithelial cell carcinogenesis by using the state of art long-read single molecular real time (SMRT) and high-throughput chromosome conformation capture (Hi-C) sequencing techniques. Systematic integration of matched SMRT, in situ Hi-C, and RNA-seq datasets revealed the complicated dynamic interplay of SVs and 3D chromosome organization and their impacts on gene expression. Our studies identify and focus remodeling of chromatin folding domains associated with cross boundary SVs enabling aberrant interactions between regulatory elements. Moreover, our data also demonstrate the existence of complex genomic rearrangements associated with two key driver genes CDKN2A and SMAD4, and characterize their influence on cancer related gene expression from linear view to 3D perspective.
2022-05-01 | GSE185069 | GEO
Project description:The genome-wide chromosome conformation capture method, Hi-C, has greatly advanced our understanding of genome organization. However, its quantitative properties, including sensitivity, bias, and linearity, remain challenging to assess. Measuring these properties in vivo is difficult due to the heterogenous and dynamic nature of chromosomal interactions. Here, using Chemically Induced Chromosomal Interaction (CICI) method, we create stable intra- and inter-chromosomal interactions in G1-phase budding yeast across a broad range of contact frequencies. Hi-C analysis of these engineered cell populations demonstrates that static intra-chromosomal loops do not generate Topologically Associated Domains (TADs) and only promote 3D proximity within ~50kb flanking regions. At moderate sequencing depth, Hi-C is sensitive enough to detect interactions occurring in a few percent of cells. It also shows no inherent bias toward intra- versus inter-chromosomal interactions. Furthermore, we observe a linear relationship between Hi-C signal intensity and contact frequency. These findings illuminate the intrinsic properties of the Hi-C assay and provide a robust framework for its calibration.
2024-12-11 | GSE283767 | GEO
Project description:In the study of interphase chromosome organization, genome-wide chromosome conformation capture (Hi-C) maps are often generated using 2-dimensional (2D) monolayer cultures. These 2D cells have morphological deviations from cells that exist in 3-dimensional (3D) tissues in vivo, and may not maintain the same chromosome conformation. We used Hi-C maps to test the extent of differences in chromosome conformation between human fibroblasts grown in 2D cultures and those grown in 3D spheroids. Significant differences in chromosome conformation were found between 2D cells and those grown in spheroids. Intra-chromosomal interactions were generally increased in spheroid cells, with a few exceptions, while inter-chromosomal interactions were generally decreased. Overall, chromosomes located closer to the nuclear periphery had increased intra-chromosomal contacts in spheroid cells, while those located more centrally had decreased interactions. This study highlights the necessity to conduct studies on the topography of the interphase nucleus under conditions that mimic an in vivo environment.
2016-01-26 | GSE77237 | GEO
Project description:Chromosome conformation capture technologies have revealed important insights into genome folding. Yet, how spatial genome architecture is related to gene expression and cell fate remains unclear. We mapped comprehensively 3D chromatin organization during mouse neural differentiation in vitro and in vivo, generating the highest resolution Hi-C maps available to date. We found that transcription is correlated with chromatin insulation and long-range interactions, but dCas9-mediated activation is insufficient for creating topological domain (TAD) boundaries de novo. Additionally, we discovered long-range contacts between gene bodies of exon-rich, active genes in all cell types. During neural differentiation, contacts between active TADs become less pronounced while inactive TADs interact stronger. An extensive Polycomb network in stem cells is disrupted, while dynamic interactions between proneural transcription factors appear in vivo. Finally, cell-type specific enhancer-promoter contacts are established concomitant to gene expression. This work shows that multiple factors influence the dynamics of chromatin interactions in development.
2017-10-18 | GSE96107 | GEO
Project description:Cell-type specific transcription factors play important roles in lineage specification whereas it is largely unknown whether and how they regulate context-specific 3D chromatin structure. Herein, we comprehensively mapped 3D chromatin organization in muscle cells and uncovered master transcription factor MyoD-mediated myogenic lineage specific chromatin structures in comparison with embryonic stem cells and neuronal cells. We discovered that MyoD is significantly enriched at loop anchor and mediate numerous chromatin loops without CTCF binding. Importantly, we found MyoD-involved interactions were dramatically disrupted when MyoD was absent, implying MyoD is an indispensable factor for loop regulation. Additionally, MyoD mediated shorter, weaker and more dynamic interactions, especially enhancer - enhancer and enhancer - promoter loops. Finally, MyoD mainly regulate cell type-specific contacts which were concomitant to muscle cell specific gene expression. Collectively, we utilized high resolution Hi-C data and genetic model to prove a master transcriptional factor govern lineage specific chromatin loops. We propose that MyoD-mediated interactions are a general feature of lineage specific transcriptional factors-regulated gene expression.
2021-05-01 | GSE157339 | GEO
Project description:Genome-wide mapping of chromatin interactions at high resolution remains experimentally and computationally challenging. Here we used a low-input “easy Hi-C” protocol to map the 3D genome architecture in human neurogenesis and brain tissues and also demonstrated that a rigorous Hi-C bias-correction pipeline (HiCorr) can significantly improve the sensitivity and robustness of Hi-C loop identification at sub-TAD level, especially the enhancer-promoter (E-P) interactions. We used HiCorr to compare the high-resolution maps of chromatin interactions from 10 tissue or cell types with a focus on neurogenesis and brain tissues. We found that dynamic chromatin loops are better hallmarks for cellular differentiation than compartment switching. HiCorr allowed direct observation of cell-type- and differentiation-specific E-P aggregates spanning large neighborhoods, suggesting a mechanism that stabilizes enhancer contacts during development. Interestingly, we concluded that Hi-C loop outperforms eQTL in explaining neurological GWAS results, revealing a unique value of high-resolution 3D genome maps in elucidating the disease etiology.
2020-07-31 | GSE116825 | GEO
Project description:Recent studies have characterized the genomic structures of many eukaryotic cells, often with a focus on their relation to gene expression. So far, these studies have largely only investigated cells grown in 2D culture, although the transcriptomes of 3D cultured cells are generally closer to their in vivo phenotype. To examine the effects of spatial constraints on chromosome conformation, we investigated the genomic architecture of mouse hepatocytes grown in 2D and 3D cultures using in situ Hi-C. Our results reveal significant differences in long-range genomic interactions, notably in compartment identity and strength as well as in TAD-TAD interactions, but only minor differences at the TAD level. RNA-seq analysis reveals an up-regulation in the 3D cultured cells of those genes involved in physiological hepatocyte functions. We find that these genes are associated with only a subset of the structural changes, suggesting that the differences in genomic structure are indeed critically important for transcriptional regulation but also that there are major structural differences owing to other functions than gene expression. Overall, our results indicate that growth in 3D significantly alters longer-range genomic interactions, which may be consequential for a subset of genes that are important for the physiological functioning of the cell.
2020-09-30 | E-MTAB-8303 | biostudies-arrayexpress
Project description:Despite recent progress in mammalian 3D genome studies, it remains experimentally and computationally challenging to identify chromatin interactions genome-wide. Here we developed a highly efficient “easy Hi-C” (eHi-C) protocol that generates high-yield libraries with 0.1 million cells. After rigorous bias-correction with a significantly improved Hi-C analysis pipeline, we can directly recognize the dynamic long- and short-range chromatin loops from contact heatmaps. We compared 10 ultra-deep Hi-C or eHi-C datasets (billion- read scale) from human tissue- or cell types focusing on brain and neurogenesis. We found that H3K9me3 marks a 3D genome compartmental barrier for induced pluripotency. Dynamic chromatin loops, but not genome compartments, are hallmarks of neuronal differentiation and neuron-related diseases. Interestingly, we observed many neuron-specific enhancer-promoter looping clusters spanning Mb-scale neighborhoods, supporting a phase-separation model leading to enhancer aggregation during brain development. Taken together, our 3D genome analyses shed light on the regulation of brain development and complex neuronal diseases.
2020-06-26 | GSE115407 | GEO
Project description:Three-dimensional (3D) genome organization is thought to be important for regulation of gene expression. Chromosome conformation capture-based studies have uncovered ensemble organizational principles such as active (A) and inactive (B) compartmentalization. In addition, large inactive regions of the genome associate with the nuclear lamina, the Lamina Associated Domains (LADs). Here we investigate the dynamic relationship between A/B-compartment organization and the 3D organization of LADs. Using refined algorithms to identify active (A) and inactive (B) compartments from Hi-C data and to define LADs from DamID, we confirm that the LADs correspond to the B-compartment. Using specialized chromosome conformation paints, we show that LAD and A/B-compartment organization are dependent upon chromatin state and A-type lamins. By integrating single-cell Hi-C data with live cell imaging and chromosome conformation paints, we demonstrate that self-organization of the B-compartment within a chromosome is an early event post-mitosis and occurs prior to organization of these domains to the nuclear lamina.
2020-03-27 | GSE124205 | GEO