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Homo sapiens
9 Downloadable Samples
Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Histone deacetylases (HDACs) and acetyltransferases control the epigenetic regulation of gene expression through modification of histone marks. Histone deacetylase inhibitors (HDACi) are small molecules that interfere with histone tail modification thus altering chromatin structure and epigenetically controlled pathways. They promote apoptosis in proliferating cells and are promising anti-cancer drugs. While some HDACis have already been approved for therapy and others are in different phases of clinical trials, the exact mechanism of action of this drug class remains elusive. Previous studies have shown that HDACis cause massive changes in chromatin structure but only moderate changes in gene expression. To which extent these changes manifest at the protein level has never been investigated on a proteome-wide scale. Here, we have studied HDACi-treated cells by large-scale mass spectrometry based proteomics. We show that HDACi treatment affects primarily the nuclear proteome and induces a selective decrease of bromodomain containing proteins (BCPs), the main readers of acetylated histone marks. By combining time-resolved proteome and transcriptome profiling, we show that BCPs are affected at the protein level as early as 12 hours after HDACi treatment and that their abundance is regulated by a combination of transcriptional and post-transcriptional mechanisms. Using gene silencing, we demonstrate that the decreased abundance of BCPs is sufficient to mediate important transcriptional changes induced by HDACi. Our data reveals a new aspect of the mechanism of action of HDACi that is mediated by an interplay between histone acetylation and the abundance of BCPs.
Publication Title
Histone Deacetylase Inhibitors (HDACi) Cause the Selective Depletion of Bromodomain Containing Proteins (BCPs).
Sample Metadata Fields
Cell line, Treatment, Time
View Samples- Mus musculus
- 4 Downloadable Samples
Illumina Genome Analyzer IIx
Description
No description.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 6 Downloadable Samples
- Illumina HiSeq 2000
Description
DNA Topoisomerase I (Top1) relaxes DNA supercoiling and is inhibited with high specificity by camptothecin, a natural product of chinese tree Camptotheca acuminata with anticancer activity. Topoisomerase activity is required at transcribing regions to modulate DNA supercoils generated by RNA polymerases. However, Top1 functions at promoters and molecular responses to CPT are not fully understood. We found that camptothecin increases antisense RNA polymerase II transcripts at active divergent CpG-island promoters in a replication-independent manner. Kinetics investigations of the formation of Top1-DNA cleavage complexes and non-B DNA structures showed that CPT interferes with Top1 modulation of negative DNA supercoiling at promoters. The present findings will be a resource to establish the role of such antisense RNAs in transcription regulation and to discover additional components of the response pathway. Moreover, the transcriptional camptothecin effects can be the molecular basis of the therapeutic activity in cancer as well as neurological syndromes.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples
SRP111915- Homo sapiens
- 112 Downloadable Samples
- NextSeq 500
Description
The human MDA MB 231 breast cancer and MDA MB 435 melanoma cell lines were selected for isolates able to pass through narrow 3 micron pores in Transwell tissue culture inserts. In addition, MDA MB 231 breast cancer cells were selected for a population of small sized cells in parallel by flow cytometric sorting. RNA sequencing of the three populations (parental, selected, flow sorted) of MDA MB 231 breast cancer cells, and two populations (parental, selected) of MDA MB 435 melanoma cells, was performed.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Age, Specimen part, Disease, Cell line, Race
View Samples SRP081135- Mus musculus
- 12 Downloadable Samples
- NextSeq 500
Description
Pancreatic cancer patient survival is the lowest of all common cancers. Given that pancreatic cancer therapies do little to improve survival, there is a significant need to identify additional potential therapeutic targets and treatment strategies. The ROCK1 locus on chromosome 18 is amplified in 15% of pancreatic patient tumors (Biankin et al. 2012), accompanied by concordant copy number/gene expression changes (Bailey et al. 2016). The ROCK1 and ROCK2 kinases promote actomyosin contractility through phosphorylation of substrates including the myosin regulatory light chain 2 (MLC2), myosin-binding subunit of the MLC phosphatase (MYPT1) and LIM kinases 1&2 (Rath and Olson 2012, Julian and Olson 2014). In addition to direct effects on the organization and dynamics of the actin cytoskeleton that impact cell morphology, ROCK-mediated cell contractility also affects gene transcription (Sanz-Moreno et al. 2011). How ROCK-mediated actomyosin contractility might contribute to pancreatic cancer by altering gene expression has not been established.In this study, mouse pancreatic ductal adenocarcinoma tumour cells were transduced with retrovirus encoding conditionally-activated estrogen-receptor hormone-binding domain (hbER) fusions with ROCK1 (ROCK1:ER) or ROCK2 (ROCK2:ER) kinase domains, or green fluorescent protein (GFP:ER). GFP:ER expressing cells were treated with ethanol vehicle or 1 micromolar 4-hydroxytamoxifen (4HT) to identify any effects of the estrogen analogue, while ROCK1:ER and ROCK2:ER cells were treated with 1 micromolar 4HT to activate the ER fusion proteins. RNA was isolated, and enriched for poly A+ transcripts prior to sequencing.Bailey, P., et al. (2016). Nature 531: 47-52.Biankin, A. V., et al. (2012). Nature 491: 399-405.Julian, L. and M. F. Olson (2014). Small GTPases 5: e29846.Rath, N. and M. F. Olson (2012). EMBO Rep 13: 900-908.Sanz-Moreno, V., et al. (2011). Cancer Cell 20: 229-245.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Immune interferon beta and gamma are essential for mammalian host defence against intracellular pathogens.
Publication Title
GBPs Inhibit Motility of Shigella flexneri but Are Targeted for Degradation by the Bacterial Ubiquitin Ligase IpaH9.8.
Sample Metadata Fields
Cell line
View Samples- Homo sapiens
- 8 Downloadable Samples
- IlluminaGenomeAnalyzerII
Description
No description.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Danio rerio
- 1 Downloadable Sample
- IlluminaHiSeq2500
Description
transcriptional profile of both macrophages (M) and endothelial end cells (EC) between three different lesion stages (uninjured control (con), upon macrophage arrival (arr), and during macrophage traction (tra)).
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Arabidopsis thaliana
- 18 Downloadable Samples
- Affymetrix Arabidopsis ATH1 Genome Array (ath1121501)
Description
Umkirch-1/Umkirch-3 hybrid plants and their parents were grown at 23SD and then shifted to 16SD for five days. 10 plants were pooled in each of three sample replicates.
Publication Title
Autoimmune response as a mechanism for a Dobzhansky-Muller-type incompatibility syndrome in plants.
Sample Metadata Fields
Specimen part
View Samples- Pseudomonas aeruginosa
- 18 Downloadable Samples
- Illumina HiSeq 2500
Description
RNASeq time course (1,2,3 hrs) of Pseudomonas aeruginosa (UCBPP-PA14) on plastic (polystyrene) petri dish
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Cell line
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