RNA-Seq of yeast W303a and YKH045 strains to investigate role of Fun30 in chromatin remodelling and centromere function
Ontology highlight
ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
SUBMITTER: Felix Krueger
PROVIDER: E-MTAB-955 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:To investigate the role of Fun30 in centromere establishment and function
2012-07-27 | E-MTAB-759 | biostudies-arrayexpress
Project description:To investigate the role of Fun30 in centromere establishment and function. Part of experiments series: DNA-seq E-MTAB-759 and RNA-seq E-MTAB-955
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Project description:In this study, we mapped for the first time differences in transcription binding among individuals and elucidated the genetic basis of such variation. Whole-genome Ste12 binding profiles were determined using ChIP-Seq in pheromone-treated cells of 43 segregants of a cross between two highly diverged yeast strains, YJM789 and S288c as well as the parental lines. We identified extensive Ste12 binding variation among individuals and mapped underlying cis- and trans- acting loci responsible for such variation. We showed that the majority of TF binding variation is cis-linked and that many variations are associated with polymorphisms residing in the binding motifs of Ste12 as well as those of several known and proposed Ste12 cofactors. We also identified two trans factors, AMN1 and FLO8, that modulate Ste12 binding to promoters of more than 10 genes under α-factor treatment. Neither of these two genes was known to regulate Ste12 previously, and we suggest that they may be key mediators of gene activity and phenotypic diversity. Ste12 binding strongly correlates with gene expression for more than 200 genes indicating that binding variation is functional. Many of the variable bound genes are involved in cell wall organization and biogenesis. Overall, we identified key regulators of molecular diversity among individuals and provide novel insights into mechanisms of gene regulation. Two ChIP-Seq experiments and one Input DNA-Seq experiment for the yeast strains S96, HS959 and 43 MATa segregants were performed under alpha factor treatment conditions; an additional replicate was also performed for some of the strains. One ChIP-Seq experiment for each parental strain was performed without alpha factor treatment, and one ChIP-Seq experiment for each of the 24 deletion strains was performed under alpha factor treatment.
2010-02-18 | E-GEOD-19635 | biostudies-arrayexpress
Project description:The identification of cancer drivers is a major goal of current cancer research. Finding driver genes within large chromosomal events is especially challenging because such alterations encompass many genes. Previously, we demonstrated that zebrafish malignant peripheral nerve sheath tumors (MPNSTs) are highly aneuploid, much like human tumors. In this study, we examined 147 zebrafish MPNSTs by massively parallel sequencing and identified both large and focal copy number alterations (CNAs). Given the low degree of conserved synteny between fish and mammals, we reasoned that comparative analyses of CNAs from fish versus human MPNSTs would enable elimination of a large proportion of passenger mutations, especially on large CNAs. Accordingly, we found less than one third of the human CNA genes were co-gained or co-lost in zebrafish, dramatically narrowing the list of candidate cancer drivers for both focal and large CNAs. We conclude that zebrafish-human comparative analysis represents a powerful, and broadly applicable, tool to enrich for evolutionarily conserved cancer drivers. --- This filing comprises data related to GEO entry GSE23666 ("Highly Aneuploid Zebrafish Malignant Peripheral Nerve Sheath Tumors have Genetic Alterations Similar to Human Cancers"), representing a followup study. 147 pairs of zebrafish (Danio rerio) tumor (MPNST) and normal tail control samples
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Project description:Aneuploidy is a hallmark of human cancers, but most mouse cancer models lack the extensive aneuploidy seen in many human tumors. The zebrafish is becoming an increasingly popular model for studying cancer. Here we report that malignant peripheral nerve sheath tumors (MPNSTs) that arise in zebrafish as a result of mutations in either ribosomal protein (rp) genes or in p53 are highly aneuploid. Karyotyping reveals that these tumors frequently harbor near-triploid numbers of chromosomes, and they vary in chromosome number from cell-to-cell within a single tumor. Using array CGH (aCGH) we found that, as in human cancers, certain fish chromosomes are preferentially over-represented while others are under-represented in many MPNSTs. In addition, we detected evidence for recurrent sub-chromosomal amplifications and deletions that may contain genes involved in cancer initiation or progression. One striking amplification included the c-met proto-oncogene. Our results suggest that the zebrafish may be a valuable model in which to study aneuploidy in human cancer and in which to identify candidate genes that may act as drivers in fish and potentially also in human tumors. For GSM587250-GSM587255: This Illumina sequencing data is for validation of a larger array-CGH dataset (GSM580580-GSM580621). For GSM580580-GSM580621: Two-condition (x3) experiment: (1) genomic DNA: MPNST (rp gene mutation) vs normal tail : 31 replicates; (2) MPNST (p53 mutation) vs normal tail: 5 replicates; (3) normal tail vs. normal tail (6 replicates) For GSM587250-GSM587255: Six samples total, in three pairs of tumor (MPNST) and normal tail control
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