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Doxorubicin Changes the Spatial Organization of the Genome around Active Promoters

ABSTRACT: To investigate the function of TOP2 on chromatin structure of human cells, we performed Hi-C using chromatin obtained from RPE1 cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE214912 | GEO | 2023/03/31

REPOSITORIES: GEO

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Doxorubicin Changes the Spatial Organization of the Genome around Active Promoters

Project description:To investigate the function of the TOP2 inhibitors treatment in binding of chromatin architecture factors, we performed ChIP-seq. We used chromatin from RPE1 cells treated with four different conditions: control (DMSO-treatment), doxorubicin treatment (200 nM and 340 nM) and ICRF193 treatment (5uM).

2023-03-31 | GSE215318 | GEO

Doxorubicin Changes the Spatial Organization of the Genome around Active Promoters

Project description:This SuperSeries is composed of the SubSeries listed below.

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Doxorubicin Changes the Spatial Organization of the Genome around Active Promoters

Project description:To investigate the function of the doxorubicin treatment in differentiation expression of human genes, we performed gene expression profiling analysis using data obtained from RNA-seq of three different conditions: control (DMSO-treatment) and doxorubicin treatment (200 nM and 340 nM).

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Doxorubicin enhances nucleosome turnover around promoters

Project description:We use a metabolic labeling strategy for directly measuring nucleosome turnover to examine the effect of doxorubicin on chromatin dynamics in squamous cell carcinoma cell lines derived from genetically defined mice. We find that doxorubicin enhances nucleosome turnover around gene promoters, and turnover correlates with gene expression level. Keywords: Chromatin affinity-purification on microarray 26 CATCH-IT arrays and 8 expression arrays.

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Doxorubicin enhances nucleosome turnover around promoters

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Doxorubicin enhances nucleosome turnover around promoters.

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Spatial chromosome folding and active transcription drive DNA fragility and formation of oncogenic MLL translocations [RNA-Seq]

Project description:How spatial chromosome organization influences genome integrity is still poorly understood. Here we show that DNA double-strand breaks (DSBs) mediated by topoisomerase 2 (TOP2) activities, are enriched at chromatin loop anchors with high transcriptional activity. Recurrent DSBs occur at CTCF/cohesin bound sites at the bases of chromatin loops and their frequency positively correlates with transcriptional output and directionality. The physiological relevance of this preferential positioning is indicated by the finding that genes recurrently translocating to drive leukemias, are highly transcribed and are enriched at loop anchors. These genes accumulate DSBs at recurrent hot spots that give rise to chromosomal fusions relying on the activity of both TOP2 isoforms and on transcriptional elongation. We propose that transcription and 3D chromosome folding jointly pose a threat to genomic stability, and are key contributors to the occurrence of genome rearrangements that drive cancer.

2019-06-12 | GSE121741 | GEO

Spatial chromosome folding and active transcription drive DNA fragility and formation of oncogenic MLL translocations [BLISS-Seq]

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Chromosomal translocations are guided by the spatial organization of the genome

Project description:The extent to which the three-dimensional organization of the genome contributes to chromosomal translocations is an important question in cancer genomics. We now have generated a high-resolution Hi-C spatial organization map of the G1-arrested mouse pro-B cell genome and mapped translocations from target DNA double-strand breaks (DSBs) within it via high-throughput genome-wide translocation sequencing. RAG endonuclease-cleaved antigen-receptor loci are dominant translocation partners for target DSBs regardless of genomic position, reflecting high frequency DSBs at these loci and their co-localization in a fraction of cells. To directly assess spatial proximity contributions, we normalized genomic DSBs via ionizing-radiation. Under these conditions, translocations were highly enriched in cis along single chromosomes containing target DSBs and within other chromosomes and sub-chromosomal domains in a manner directly related to pre-existing spatial proximity. Our studies reveal the power of combining two high-throughput genomic methods to address long-standing questions in cancer biology. Hi-C interaction maps for WT and ATM -/- G1-arrested AMuLV-transformed pro-B cell lines.

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Differential Contribution of Steady-State RNA and Active Transcription in Chromatin Organization

Project description:Nuclear RNA and the act of transcription have been implicated in nuclear organization. However, their global contribution to shaping fundamental features of higher-order genome structure such as topologically associated domains (TADs) and genomic compartments remains unclear. To investigate these questions, we perform Hi-C genome-wide chromatin conformation capture in the presence and absence of RNase before and after crosslinking, or a transcriptional inhibitor. TAD boundaries are largely unaffected by RNase treatment, whereas transcriptional inhibition leads to higher inter-TAD interactions. Collectively, our findings demonstrate differences in the relative contribution of RNA and transcription to the formation of TAD boundaries detected by the widely used Hi-C methodology.

2019-04-01 | GSE114337 | GEO

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