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Chromosome conformation capture-on-chip of glucocorticoid receptor-responsive loci in mouse cells

ABSTRACT: The spatial organization of genes in the interphase nucleus plays an important role in establishment and regulation of gene expression. Contradicting results have been reported to date, with little consensus about the dynamics of nuclear organization and the features of the contact loci. In this study we investigated the properties and dynamics of genomic loci that are in contact with glucocorticoid receptor (GR)-responsive loci. We took a systematic approach, combining genome-wide interaction profiling by the chromosome conformation capture-on-chip (4C) technology with expression, protein occupancy, and chromatin accessibility profiles. This approach allowed a comprehensive analysis of how distinct features of the linear genome are organized in the three-dimensional nuclear space in the context of rapid gene regulation. We found that the transcriptional response to GR occurs without dramatic nuclear reorganization. Moreover, contrary to the view of transcription-driven organization, even genes with opposite transcriptional responses co-localize. Regions contacting GR-regulated genes are not particularly enriched for GR-regulated loci or for any functional group of genes, suggesting that these subnuclear environments are not organized to respond to a specific factor. The contact regions are, however, highly enriched for DNaseI hypersensitive sites which represent the entire cell type-specific regulatory sites. These findings indicate that the nucleus is pre-organized in a conformation allowing rapid transcriptional reprogramming, and suggest that a major force in shaping genome architecture is the repertoire of chromatin binding factors. Numerous open chromatin loci may be arranged in nuclear domains that are poised to respond to diverse signals in general, and to permit efficient gene regulation.

ORGANISM(S): Mus musculus

PROVIDER: GSE27115 | GEO | 2011/04/21

SECONDARY ACCESSION(S): PRJNA137579

REPOSITORIES: GEO

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Project description:The spatial organization of genes in the interphase nucleus plays an important role in establishment and regulation of gene expression. Contradicting results have been reported to date, with little consensus about the dynamics of nuclear organization and the features of the contact loci. In this study we investigated the properties and dynamics of genomic loci that are in contact with glucocorticoid receptor (GR)-responsive loci. We took a systematic approach, combining genome-wide interaction profiling by the chromosome conformation capture-on-chip (4C) technology with expression, protein occupancy, and chromatin accessibility profiles. This approach allowed a comprehensive analysis of how distinct features of the linear genome are organized in the three-dimensional nuclear space in the context of rapid gene regulation. We found that the transcriptional response to GR occurs without dramatic nuclear reorganization. Moreover, contrary to the view of transcription-driven organization, even genes with opposite transcriptional responses co-localize. Regions contacting GR-regulated genes are not particularly enriched for GR-regulated loci or for any functional group of genes, suggesting that these subnuclear environments are not organized to respond to a specific factor. The contact regions are, however, highly enriched for DNaseI hypersensitive sites which represent the entire cell type-specific regulatory sites. These findings indicate that the nucleus is pre-organized in a conformation allowing rapid transcriptional reprogramming, and suggest that a major force in shaping genome architecture is the repertoire of chromatin binding factors. Numerous open chromatin loci may be arranged in nuclear domains that are poised to respond to diverse signals in general, and to permit efficient gene regulation. Fourteen arrays total: Eight microarrays from individual biological replicates, and six microarrays each from a pool of two biological replicates. This submission represents the chromosome conformation capture-on-chip component of the study. The expression data are included in GSE26189.

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Chromosome conformation capture-on-chip of glucocorticoid receptor-responsive loci in mouse cells

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