Heterochromatin 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.
No sample metadata fields
View SamplesStudy of single and double mutants of the two roX RNAs in D. melanogaster Overall design: Study of single and double mutants of the two roX RNAs in D. melanogaster
RNA-on-X 1 and 2 in Drosophila melanogaster fulfill separate functions in dosage compensation.
Specimen part, Cell line, Subject
View SamplesThe aim was to identify genes that were commonly influenced by a siRNA targeting PRKCD in breast cancer cell lines.
Down Regulation of CLDND1 Induces Apoptosis in Breast Cancer Cells.
Cell line, Treatment
View SamplesAneuploidy, 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 SamplesThe ATP-dependent DExH/D-box helicase DHX9 is a key participant in a number of gene regulatory steps, including transcriptional, translational, microRNA-mediated control, DNA replication, and maintenance of genomic stability. DHX9 has also been implicated in maintenance of the tumorigenic process and in drug response. Here, we report that inhibition of DHX9 expression is lethal to multiple human and mouse cancer cell lines. In contrast, using a novel conditional shDHX9 mouse model, we demonstrate that sustained and prolonged suppression of DHX9 is well tolerated at the organismal level. Our results demonstrate a robust tolerance for DHX9 knockdown in non-transformed cells and supports the targeting of DHX9 as an effective and specific chemotherapeutic approach.
Tumor cell survival dependence on the DHX9 DExH-box helicase.
Specimen part
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 SamplesMicroarray based mRNA profiling was used to charactarize and compare the gene expression in cells grown as monolayer or spheroids.
Loss of cancer drug activity in colon cancer HCT-116 cells during spheroid formation in a new 3-D spheroid cell culture system.
Cell line
View SamplesAcute quadriplegic myopathy (AQM) or critical illness myopathy (CIM) is frequently observed in intensive care unit (ICU) patients. In order to elucidate duration-dependent effects of the ICU intervention on molecular and functional networks that control the muscle wasting and weakness in AQM, gene expression profile was analyzed at time points varying from 6 hours to 14 days in a unique experimental rat model mimicking ICU conditions, i.e., post-synaptically paralyzed, mechanically ventilated and extensively monitored animals.
Muscle wasting and the temporal gene expression pattern in a novel rat intensive care unit model.
Sex, Specimen part, Disease, Disease stage
View SamplesThe fallopian tube transports the gametes to the fertilization site and delivers the embryo to the uterus at the optimal time for implantation. Progesterone and the classical progesterone receptor (PGR) are known to be involved in regulating both tubal ciliary beating and muscular contractions, possibly involving both genomic and non-genomic actions. To provide more clues on the mechanisms involved, we investigated the effect of progesterone on gene expression in mice fallopian tubes in vitro at early (20 min) and later (2 h, 8 h) time-points using microarray and/or quantitative PCR. In parallel, oocyte cumulus complex transport was investigated in ovulating mice injected with one of the PGR antagonists, Org 31710 or CDB2194. Microarray analyses did not reveal any apparently regulated genes 20 min after progesterone treatment, in agreement with a proposed non-genomic action of progesterone controlling ciliary beating. After 2 h, 11 genes were significantly up-regulated. Analyses by quantitative PCR at 2 h and 8 h showed a consistent up-regulation of endothelin 1 (Edn1) and a down-regulation of its receptor Ednra by progesterone. We also show that treatment with progesterone receptor antagonist before ovulation accelerates the transport of the oocyte cumulus complex. This is the first study showing that progesterone regulates Edn1 and Ednra in the fallopian tube. Together with previous studies on endothelin-mediated effects on muscular contractions in the fallopian tube, the results from this study suggest that endothelin is a mediator of the progesterone-controlled effects on muscular contraction, and eventually gamete transport, in the fallopian tube.
Progesterone-mediated effects on gene expression and oocyte-cumulus complex transport in the mouse fallopian tube.
Sex, Specimen part, Treatment, Time
View Samples