Positioned nucleosomes limit the access of proteins to DNA and implement regulatory features encoded in eukaryotic genomes. Here we generated the first genome-wide nucleosome positioning map for Schizosaccharomyces pombe and annotated transcription start and termination sites genome-wide. Using this resource we found surprising differences compared to the nucleosome organization in the distantly related yeast Saccharomyces cerevisiae [the cerevisiae data has been published by others (PMID: 17873876) and the raw data is deposited at ArrayExpress(E-MEXP-1172)]. DNA sequence guides nucleosome positioning differently, e.g., poly(dA:dT) elements are not enriched in S. pombe nucleosome-depleted regions (NDRs). Regular nucleosomal arrays emanate more asymmetrically, i.e., mainly co-directionally with transcription, from promoter NDRs, but promoters harbouring the histone variant H2A.Z show regular arrays also upstream. Regular nucleosome phasing in S. pombe has a very short repeat length of 154 base pairs, and requires a remodeler, Mit1, conserved in humans but not found in S. cerevisiae. Nucleosome positioning mechanisms are evidently not universal but evolutionarily plastic.
Schizosaccharomyces pombe genome-wide nucleosome mapping reveals positioning mechanisms distinct from those of Saccharomyces cerevisiae.
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View SamplesWe examined genome-wide variation in transcription factor binding in different individuals and a chimpanzee using chromatin immunoprecipitation followed by massively-parallel sequencing (ChIP-Seq). The binding sites of RNA Polymerase II (Pol II) as well as a key regulator of immune responses, NFkB, were mapped in ten HapMap lymphoblastoid cell lines derived from individuals of African, European, and Asian ancestry, including a parent-offspring trio. We also mapped gene expression in all ten human cell lines for two treatment conditions: a) no treatment and b) following induction by TNF-alpha. Overall design: Genome-wide comparison of Pol II and NF-KappaB binding in ten individuals. RNA-seq study with no treatment.
Variation in transcription factor binding among humans.
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View SamplesWe examined genome-wide variation in transcription factor binding in different individuals and a chimpanzee using chromatin immunoprecipitation followed by massively-parallel sequencing (ChIP-Seq). The binding sites of RNA Polymerase II (Pol II) as well as a key regulator of immune responses, NFkB, were mapped in ten HapMap lymphoblastoid cell lines derived from individuals of African, European, and Asian ancestry, including a parent-offspring trio. We also mapped gene expression in all ten human cell lines for two treatment conditions: a) no treatment and b) following induction by TNF-alpha. Overall design: Genome-wide comparison of Pol II and NF-KappaB binding in ten individuals. RNA-seq study with TNF-alpha treatment.
Variation in transcription factor binding among humans.
No sample metadata fields
View SamplesInhibition of Brd4 with Jq1 in neurons with or without BDNF stimulation Overall design: Examination of the effects of Jq1 treatment on primary mouse cortical neurons
BET protein Brd4 activates transcription in neurons and BET inhibitor Jq1 blocks memory in mice.
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View SamplesWidespread epigenetic disruptions in FXS mice leads to transcriptional changes that likely contribute to the neuronal phenotpyes underlying FXS. Overall design: 7DIV cultured cortical neurons from WT or Fmr1 KO mice were treated for 24 hours with vehicle, Jq1, or THZ, performed in triplicate.
Excess Translation of Epigenetic Regulators Contributes to Fragile X Syndrome and Is Alleviated by Brd4 Inhibition.
Treatment, Subject
View Samples18 zero-hour and 18 selected post-transplant (Tx) biopsy samples from 18 kidney allografts (8 acute kidney injury (AKI), 10 PBx - protocol biopsies - controls) were analyzed by using the Affymetrix GeneChip Human Gene 2.0 ST Array.
Molecular biomarker candidates of acute kidney injury in zero-hour renal transplant needle biopsies.
Specimen part
View SamplesThe aim of this study was to perform comparative gene expression analysis of AIP mutation-positive, AIP mutation-negative familial and sporadic somatotroph tumours to discover the genes/pathways responsible for the aggressive phenotype.
Multi-chaperone function modulation and association with cytoskeletal proteins are key features of the function of AIP in the pituitary gland.
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View SamplesThis series includes the four major subtypes of pituitary adenomas and normal post-mortem pituitary tissue
Differential gene expression in pituitary adenomas by oligonucleotide array analysis.
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View SamplesGermline-specific RNA helicase Spindle-E (Spn-E) is known to be essential for piRNA silencing in Drosophila that takes place mainly in the perinuclear nuage granules. Loss-of-function spn-E mutations lead to tandem Stellate genes derepression in the testes and retrotransposon mobilization in the ovaries. However, Spn-E functions in the piRNA pathway are still obscure. Analysis of total library of short RNAs from the testes of spn-E heterozygous flies revealed the presence of abundant piRNA ping-pong pairs originating from Su(Ste) transcripts. The abundance of these ping-pong pairs were sharply reduced in the library from the testes of spn-E mutants. Thus we found that ping-pong mechanism contributed to Su(Ste) piRNA generation in the testes. The lack of Spn-E caused a significant drop of protein levels of key ping-pong participants, Aubergine (Aub) and AGO3 proteins of PIWI subfamily, in the germline of both males and females, but did not disrupt of their assembly in nuage granules. We found that observed decline of the protein expression was not caused by suppression of aub and ago3 transcription as well as total transcription, indicating possible contribution of Spn-E to post-transcriptional regulation. Overall design: The fractions of small RNAs (19-29 nt) from testis of Drosophila melanogaster spnE/+ spnE/- strains were sequenced using Illumina HiSeq 2000.
RNA helicase Spn-E is required to maintain Aub and AGO3 protein levels for piRNA silencing in the germline of Drosophila.
Specimen part, Subject
View SamplesIdentifying the genes underlying quantitative trait loci (QTL) for disease has proven difficult, mainly due to the low resolution of the approach and the complex genetics involved. However, recent advances in bioinformatics and the availability of genetic resources now make it possible to narrow the genetic intervals and test candidate genes. In addition to identifying the causative genes, defining the pathways that are affected by these QTL is of major importance as it can give us insight into the disease process and provide evidence to support candidate genes. In this study we mapped three significant and one suggestive QTL on Chromosomes (Chrs) 1, 4, 15, and 17, respectively, for increased albumin excretion (measured as albumin-to-creatinine ratio) in a cross between the MRL/MpJ and SM/J mouse inbred strains. By combining data from several sources and by utilizing gene expression data, we identified Tlr12 as a likely candidate for the Chr 4 QTL. Through the mapping of 33,881 transcripts measured by microarray on kidney RNA from each of the 173 male F2 animals, we identified several downstream pathways associated with these QTL. Among these were the glycan degradation, leukocyte migration, and antigen presenting pathways. We demonstrate that by combining data from multiple sources, we can identify not only genes that are likely to be causal candidates for QTL, but also the pathways through which these genes act to alter phenotypes. This combined approach provides valuable insights into the causes and consequences of renal disease.
Uncovering genes and regulatory pathways related to urinary albumin excretion.
Sex, Age
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