Dataset Information

Spatial localization of co-regulated genes exceeds genomic gene clustering in the Saccharomyces cerevisiae genome.

ABSTRACT: While it has been long recognized that genes are not randomly positioned along the genome, the degree to which its 3D structure influences the arrangement of genes has remained elusive. In particular, several lines of evidence suggest that actively transcribed genes are spatially co-localized, forming transcription factories; however, a generalized systematic test has hitherto not been described. Here we reveal transcription factories using a rigorous definition of genomic structure based on Saccharomyces cerevisiae chromosome conformation capture data, coupled with an experimental design controlling for the primary gene order. We develop a data-driven method for the interpolation and the embedding of such datasets and introduce statistics that enable the comparison of the spatial and genomic densities of genes. Combining these, we report evidence that co-regulated genes are clustered in space, beyond their observed clustering in the context of gene order along the genome and show this phenomenon is significant for 64 out of 117 transcription factors. Furthermore, we show that those transcription factors with high spatially co-localized targets are expressed higher than those whose targets are not spatially clustered. Collectively, our results support the notion that, at a given time, the physical density of genes is intimately related to regulatory activity.

SUBMITTER: Ben-Elazar S

PROVIDER: S-EPMC3575811 | biostudies-other | 2013 Feb

REPOSITORIES: biostudies-other

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Spatial localization of co-regulated genes exceeds genomic gene clustering in the Saccharomyces cerevisiae genome.

Ben-Elazar Shay S Yakhini Zohar Z Yanai Itai I

Nucleic acids research 20130108 4

While it has been long recognized that genes are not randomly positioned along the genome, the degree to which its 3D structure influences the arrangement of genes has remained elusive. In particular, several lines of evidence suggest that actively transcribed genes are spatially co-localized, forming transcription factories; however, a generalized systematic test has hitherto not been described. Here we reveal transcription factories using a rigorous definition of genomic structure based on Sac ...[more]

PMID: 23303780

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Project description:Background: Chromatin remodeling complexes facilitate the access of enzymes that mediate transcription, replication or repair of DNA by modulating nucleosome position and/or composition. Ino80 is the DNA-dependent Snf2-like ATPase subunit of a complex whose nucleosome remodeling activity requires actin-related proteins, Arp4, Arp5 and Arp8, as well as two RuvB-like DNA helicase subunits. Budding yeast mutants deficient for Ino80 function are not only hypersensitive to reagents that induce DNA double strand breaks, but also to those that impair replication fork progression. Results: To understand why ino80 mutants are sensitive to agents that perturb DNA replication, we used chromatin immunoprecipitation to map the binding sites of the Ino80 chromatin remodeling complex on four budding yeast chromosomes. We found that Ino80 and Arp5 binding sites coincide with origins of DNA replication and tRNA genes. In addition, Ino80 was bound at 67% of the promoters of genes that are sensitive to ino80 mutation. When replication forks were arrested near origins in the presence of hydroxyurea (HU), the presence of the Ino80 complex at stalled forks and at unfired origins increased dramatically. Importantly, the resumption of DNA replication after release from a HU block was impaired in the absence of Ino80 activity. Mutant cells accumulated double-strand breaks as they attempted to restart replication. Consistently, ino80-deficient cells, although proficient for checkpoint activation, delay recovery from the checkpoint response. Conclusions: The Ino80 chromatin remodeling complex is enriched at stalled replication forks where it promotes the resumption of replication upon recovery from fork arrest. Keywords: ChIP-chip • The goal of the experiment Genome-wide localization of Ino80 on chromosome in Saccharomyces cerevisiae • Keywords DNA replication, Saccharomyces cerevisiae, Genome tilling array (chromosome III, IV, V, VI) • Experimental factor Distribution of Ino80 in random culture Distribution of Ino80 in G1 phase Distribution of Ino80 in early S phase • Experimental design ChIP analyses: W303 background cells expressing Myc-tagged Ino80 were used for the ChIP using anti-Myc monoclonal antibody (9E11). ChIP-chip analyses: In all cases, hybridization data for ChIP fraction was compared with WCE (whole cell extract) fraction. Saccharomyces cerevisiae affymetrix genome tiling array (SC3456a520015F for chromosome III, IV, V, VI) was used. • Quality control steps taken Confirmation of several loci by quantitative real time PCR.

Dataset Information

Spatial localization of co-regulated genes exceeds genomic gene clustering in the Saccharomyces cerevisiae genome.

Publications

Spatial localization of co-regulated genes exceeds genomic gene clustering in the Saccharomyces cerevisiae genome.

Similar Datasets

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