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The Properties of Genome Conformation and Spatial Gene Interaction and Regulation Networks of Normal and Malignant Human Cell Types

ABSTRACT: In this work, we generated hundreds of millions of Hi-C paired end sequence reads for three different human cells (RL follicular lymphoma cell line, primary tumor B-cells from an acute lymphoblastic leukemia patient, and MHH-CALL-4 B-cell acute lymphoblastic leukemia cell line) using the Hi-C technique. An in-house Bioinformatics software pipeline was developed and applied to map sequence reads to the human reference genome, producing a large data set of high-quality and high-resolution chromosome contacts. Our computational analysis on these data reveal some interesting properties of human genome conformation, including conformational conservation and variation of the genomes of different cells, intra- and inter-chromosomal interactions, aberrant chromosomal translocation, spatial gene clusters, spatial gene-gene interactions, and spatial gene-regulatory-element interaction. Furthermore, we derived spatial interactions between functional elements (genes, transcription factor binding sites) from the chromosomal interaction data. The data were then used to generate chromosome-/genome-wide gene-gene interaction networks, transcription factor binding site (TFBS) – TFBS networks, and gene-TFBS networks. Remarkably, the connectivity in both networks shows the hallmark features of scale-free networks, suggesting that spatial interactions of gene-gene, gene-TFBS, and TFBS-TFBS in a genome are far from random.

ORGANISM(S): Homo sapiens

PROVIDER: GSE73924 | GEO | 2015/11/01

SECONDARY ACCESSION(S): PRJNA298525

REPOSITORIES: GEO

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The Properties of Genome Conformation and Spatial Gene Interaction and Regulation Networks of Normal and Malignant Human Cell Types

Project description:In this work, we generated hundreds of millions of Hi-C paired end sequence reads for three different human cells (RL follicular lymphoma cell line, primary tumor B-cells from an acute lymphoblastic leukemia patient, and MHH-CALL-4 B-cell acute lymphoblastic leukemia cell line) using the Hi-C technique. An in-house Bioinformatics software pipeline was developed and applied to map sequence reads to the human reference genome, producing a large data set of high-quality and high-resolution chromosome contacts. Our computational analysis on these data reveal some interesting properties of human genome conformation, including conformational conservation and variation of the genomes of different cells, intra- and inter-chromosomal interactions, aberrant chromosomal translocation, spatial gene clusters, spatial gene-gene interactions, and spatial gene-regulatory-element interaction. Furthermore, we derived spatial interactions between functional elements (genes, transcription factor binding sites) from the chromosomal interaction data. The data were then used to generate chromosome-/genome-wide gene-gene interaction networks, transcription factor binding site (TFBS) â TFBS networks, and gene-TFBS networks. Remarkably, the connectivity in both networks shows the hallmark features of scale-free networks, suggesting that spatial interactions of gene-gene, gene-TFBS, and TFBS-TFBS in a genome are far from random. Three different human cells (RL follicular lymphoma cell line, primary tumor B-cells from an acute lymphoblastic leukemia patient, and MHH-CALL-4 B-cell acute lymphoblastic leukemia cell line) were analyzed

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2024-09-16 | PXD048222 | Pride

Higher-order inter-chromosomal hubs shape 3-dimensional genome organization in the nucleus

Project description:We develop Split-Pool Recognition of Interactions by Tag Extension (SPRITE), which enables genome-wide detection of higher-order interactions that occur simultaneously within the nucleus in a proximity-ligation independent manner. We generated SPRITE maps in two mammalian cell types – mouse embryonic stem cells (mES) and human lymphoblastoid cells (GM12878). We generated ~1.5 billion sequencing reads from each sample and recapitulate known genome structures identified by Hi-C, including chromosome territories, compartments, topologically associated domains, and loop structures, and identify that many of these occur within higher-order structures in the nucleus. Because SPRITE does not rely on proximity-ligation, we find that SPRITE identifies interactions that occur across larger spatial distances than can be observed by Hi-C. These long-range interactions include two major hubs of inter-chromosomal interactions. We extended SPRITE to enable simultaneous measurements of RNA and DNA interactions and observe ribosomal RNA interactions across specific regions on the genome that correspond to DNA organization around the nucleolus. We show that gene-dense regions that are highly transcribed by PolII organize around nuclear speckles and gene poor, and therefore transcriptionally inactive, regions that are centromere-proximal organize around the nucleolus. In addition to the regions that directly associate around these nuclear bodies, we find that a substantial fraction of the genome exhibits preferential spatial positioning in the nucleus relative to each of these nuclear bodies and that the spatial preferences identified by SPRITE are highly correlated with 3D distances measured by microscopy.

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2015-09-02 | E-GEOD-66733 | biostudies-arrayexpress

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Project description:Extrachromosomal, circular DNA (ecDNA) is emerging as a prevalent yet less characterized oncogenic alteration in cancer genomes. We leverage ChIA-PET and ChIA-Drop chromatin interaction assays to characterize genome-wide ecDNA-mediated chromatin contacts that impact transcriptional programs in cancers. ecDNAs in glioblastoma patient-derived neurosphere and prostate cancer cell cultures are marked by widespread intra-ecDNA and genome-wide chromosomal interactions. ecDNA-chromatin contact foci are characterized by broad and high-level H3K27ac signals converging predominantly on chromosomal genes of increased expression levels. Prostate cancer cells harboring synthetic ecDNA circles composed of characterized enhancers result in the genome-wide activation of chromosomal gene transcription. Deciphering the chromosomal targets of ecDNAs at single-molecule resolution reveals an association with actively expressed oncogenes spatially clustered within ecDNA-directed interaction networks. Our results suggest that ecDNA can function as mobile transcriptional enhancers to promote tumor progression and manifest a potential synthetic aneuploidy mechanism of transcription control in cancer.

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