Aneuploidy, i.e., variation in the number of individual chromosomes (chromosomal aneuploidy) or chromosome segment (segmental aneuploidy) is associated with developmental abnormalities and reduced fitness in all species examined, is the leading cause of miscarriages and mental retardations and a hallmark of cancer. Despite their documented importance in disease the effects of aneuploidies on the transcriptome remains largely unknown. Here we have examined the expression output in seven deficiency heterozygotes as single deficiencies and in all pairwise combinations. The results show that genes in one copy are buffered, i.e., are expressed above the expected 50% expression level compared to wild type and the buffering is general and not influenced by additional haploid regions. Long genes are significantly better buffered than short genes and our analysis suggests that gene length is the primary determinant for the degree of buffering. For short genes the degree of buffering depends on expression level and expression pattern. Furthermore, the results show that in deficiency heterozygotes the expression of genes involved in proteolysis is enhanced and negatively correlates with the degree of buffering. Our results suggest that proteolysis is a general response induced by aneuploidy.
Buffering and proteolysis are induced by segmental monosomy in Drosophila melanogaster.
Sex
View SamplesChromosomal instability which involves deletion and duplication of chromosomes or chromosome parts is a common feature of cancers, and deficiency screens are commonly used as a method to find genes involved in different biological pathways. Still, how gene expression from whole chromosomes or large chromosomal domains is affected by deficiencies, duplications or chromosome loss is largely unknown. Using expression microarrays of deficiency hemizygotes and a duplication hemizygote we show that expressed genes are significantly buffered when present in a deficiency hemizygote and that the buffering effect is general and not mainly caused by feedback regulation of individual genes. Differentially expressed genes are in general better buffered than ubiquitously expressed genes when present in one copy. When present in three copies, differentially expressed genes are in general less buffered than ubiquitously expressed genes. Furthermore, we show that the 4th chromosome is compensated in response to dose differences. Our results suggest that general mechanisms exist to stimulate and to repress gene expression of aneuploidy regions and on the 4th chromosome this compensation is mediated by POF (Painting of Fourth).
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View SamplesHeterochromatin protein 1a (HP1a) is a chromatin associated protein that has been well studied in many model organisms, such as Drosophila, where it is a determining factor for classical heterochromatin. HP1a is associated with the two histone methyltransferases SETDB1 and Su(var)3-9, which mediate H3K9 methylation marks and participate in the establishment and spreading of HP1a enriched chromatin. While HP1a is generally regarded as a factor that represses gene transcription, several reports have linked HP1a binding to active genes, and in some cases, it has been shown to stimulate transcriptional activity. To clarify the function of HP1a in transcription regulation and its association with Su(var)3-9, SETDB1 and the chromosome 4 specific protein POF, we conducted genome-wide expression studies and combined the results with available binding data in Drosophila melanogaster. The results suggested that HP1a has a repressing function on chromosome 4, where it preferentially targets non-ubiquitously expressed genes (NUEGs), and a stimulating function in pericentromeric regions. Further, we showed that the effects of SETDB1 and Su(var)3-9 are similar to HP1a, and on chromosome 4, Su(var)3-9, SETDB1 and HP1a target the same genes. In contrast, transposons are repressed by HP1a and Su(var)3-9 but are un-affected by SETDB1 and POF. In addition, we found that the binding level and expression effects of HP1a are affected by gene length. Our results indicate that genes have adapted to be properly expressed in their local chromatin environment.
HP1a, Su(var)3-9, SETDB1 and POF stimulate or repress gene expression depending on genomic position, gene length and expression pattern in Drosophila melanogaster.
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View SamplesAnalysis of expression in pof mutant and wt 1st instar larvae
Painting of fourth and chromosome-wide regulation of the 4th chromosome in Drosophila melanogaster.
Sex, Specimen part
View SamplesAnalysis of gene expression in pof deletion mutants. Chromosome 4 genes are down-regulated in pof mutants compared to wildtype control. 200 Drosophila melanogaster first instar larvae were used for each of three biological replicates of y1 w67c23; PofD119/PofD119 and three biological replicates of y1 w67c23 as controls.
Painting of fourth and chromosome-wide regulation of the 4th chromosome in Drosophila melanogaster.
Sex, Specimen part
View SamplesTo study the influence of POF on transcription in testis we made expression arrays from dissected testes (Pof mutants and wild type control). It is clear that POF mainly alters the expression of genes on the fourth chromosome
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View SamplesThe purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1b treatment (Betaferon, 250 g every other day) in patients with relapsing-remitting form of multiple sclerosis (MS).
Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View SamplesGene expression profile comparison from fibroblasts of Huntington individuals and normal ones
Gene expression profile in fibroblasts of Huntington's disease patients and controls.
Sex, Age, Specimen part, Disease
View SamplesComparison of the differential expression mRNA profiles from the brain cortex of hypoxia and normaixa rats by silica microarray chip
No associated publication
Specimen part
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