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Locus-specific and activity-independent gene repositioning during early tumorigenesis.

ABSTRACT: The mammalian genome is highly organized within the cell nucleus. The nuclear position of many genes and genomic regions changes during physiological processes such as proliferation, differentiation, and disease. It is unclear whether disease-associated positioning changes occur specifically or are part of more global genome reorganization events. Here, we have analyzed the spatial position of a defined set of cancer-associated genes in an established mammary epithelial three-dimensional cell culture model of the early stages of breast cancer. We find that the genome is globally reorganized during normal and tumorigenic epithelial differentiation. Systematic mapping of changes in spatial positioning of cancer-associated genes reveals gene-specific positioning behavior and we identify several genes that are specifically repositioned during tumorigenesis. Alterations of spatial positioning patterns during differentiation and tumorigenesis were unrelated to gene activity. Our results demonstrate the existence of activity-independent genome repositioning events in the early stages of tumor formation.

SUBMITTER: Meaburn KJ

PROVIDER: S-EPMC2213600 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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Locus-specific and activity-independent gene repositioning during early tumorigenesis.

Meaburn Karen J KJ Misteli Tom T

The Journal of cell biology 20080101 1

The mammalian genome is highly organized within the cell nucleus. The nuclear position of many genes and genomic regions changes during physiological processes such as proliferation, differentiation, and disease. It is unclear whether disease-associated positioning changes occur specifically or are part of more global genome reorganization events. Here, we have analyzed the spatial position of a defined set of cancer-associated genes in an established mammary epithelial three-dimensional cell cu ...[more]

PMID: 18195100

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Project description:Polyploidization is a fundamental process in plant evolution. One of the biggest challenges faced by a new polyploid is meiosis, particularly discriminating between multiple related chromosomes so that only homologous chromosomes synapse and recombine to ensure regular chromosome segregation and balanced gametes. Despite its large genome size, high DNA repetitive content and similarity between homoeologous chromosomes, hexaploid wheat completes meiosis in a shorter period than diploid species with a much smaller genome. Therefore, during wheat meiosis, mechanisms additional to the classical model based on DNA sequence homology, must facilitate more efficient homologous recognition. One such mechanism could involve exploitation of differences in chromosome structure between homologs and homoeologs at the onset of meiosis. In turn, these chromatin changes, can be expected to be linked to transcriptional gene activity. In this study, we present an extensive analysis of a large RNA-seq data derived from six different genotypes: wheat, wheat-rye hybrids and newly synthesized octoploid triticale, both in the presence and absence of the Ph1 locus. Plant material was collected at early prophase, at the transition leptotene-zygotene, when the telomere bouquet is forming and synapsis between homologs is beginning. The six genotypes exhibit different levels of synapsis and chromatin structure at this stage; therefore, recombination and consequently segregation, are also different. Unexpectedly, our study reveals that neither synapsis, whole genome duplication nor the absence of the Ph1 locus are associated with major changes in gene expression levels during early meiotic prophase. Overall wheat transcription at this meiotic stage is therefore highly resilient to such alterations, even in the presence of major chromatin structural changes. Further studies in wheat and other polyploid species will be required to reveal whether these observations are specific to wheat meiosis.

Dataset Information

Locus-specific and activity-independent gene repositioning during early tumorigenesis.

Publications

Locus-specific and activity-independent gene repositioning during early tumorigenesis.

Similar Datasets

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