Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Chromatin structure changes upon oxidative stress or UV irradiation in the yeast Saccharomyces cerevisiae

ABSTRACT: Development of molecular approaches based on chromosome conformation capture (3C) technology such as Hi-C, combined with methods for modeling and interpreting chromatin interaction data, have revolutionized the analysis of chromosome folding. Even if the impact of chromatin structure on gene expression seems likely, little is known about the dynamics of DNA compaction and the factors involved in this process still have to be determined. Using the yeast Saccharomyces cerevisiae as a model, we used Hi-C technology to evaluate how 3D chromatin structure changes during different cellular processes such as adaptation in response to stress or DNA repair. We optimized the protocol from Belton, J.M et al (1) to produce our Hi-C libraries, one from control cells, one from cells after oxidative stress and one from cells after UV irradiation. Preliminary analysis suggests that in response to oxidative stress, chromosomes tend to make more contacts in trans and less contacts in cis compared to normal condition.

INSTRUMENT(S): Illumina HiSeq 2000

ORGANISM(S): Saccharomyces cerevisiae

SUBMITTER: Diana Buitrago

PROVIDER: E-MTAB-5825 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:The development of the human malaria parasite Plasmodium falciparum is controlled by coordinated changes in gene expression throughout its complex life cycle, but the corresponding regulatory mechanisms are incompletely understood. To study the relation between genome architecture and gene regulation in Plasmodium, we studied the genome structure of P. falciparum at three time points during its erythrocytic (asexual) cycle. Using chromosome conformation capture coupled with next-generation sequencing technology (Hi-C), we obtained high-resolution chromosomal contact maps, which we then used to construct a consensus three-dimensional genome structure for each time point. We observe strong clustering of centromeres, telomeres, ribosomal DNA and virulence genes, resulting in a complex architecture that cannot be explained by a simple volume exclusion model. Internal virulence gene clusters appear to be an important factor in shaping the genome architecture as they exhibit domain-like structures similar to topological domains in mammalian genomes. Midway during the cell cycle, at the highly transcriptionally active trophozoite stage, the genome adopts a more open chromatin structure with increased chromosomal intermingling. In addition, we observed reduced expression of genes located in spatial proximity to the repressive subtelomeric center, and colocalization of distinct groups of parasite-specific genes with coordinated expression profiles. Overall, our results are indicative of a strong association between the P. falciparum spatial genome organization and gene expression. Understanding the molecular processes involved in genome conformation dynamics could contribute to the discovery of novel antimalarial strategies. Analysis of the spatial organization of the P. falciparum genome at three stages of the erythrocytic cycle using chromosome conformation capture coupled with next generation sequencing (Hi-C). As a control, we included one sample for which chromatin contacts were not preserved by crosslinking of DNA and proteins.

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Chromatin structure changes upon oxidative stress or UV irradiation in the yeast Saccharomyces cerevisiae

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