Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Restrictions in amino acid availability revealed by differential ribosome codon reading

ABSTRACT: This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

ORGANISM(S): Homo sapiens

SUBMITTER: Koos Rooijers

PROVIDER: E-GEOD-59821 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Tumour-specific proline vulnerability uncovered by differential ribosome codon reading.

Loayza-Puch Fabricio F Rooijers Koos K Buil Levi C M LC Zijlstra Jelle J Oude Vrielink Joachim F JF Lopes Rui R Ugalde Alejandro Pineiro AP van Breugel Pieter P Hofland Ingrid I Wesseling Jelle J van Tellingen Olaf O Bex Axel A Agami Reuven R

Nature 20160215 7591

Tumour growth and metabolic adaptation may restrict the availability of certain amino acids for protein synthesis. It has recently been shown that certain types of cancer cells depend on glycine, glutamine, leucine and serine metabolism to proliferate and survive. In addition, successful therapies using L-asparaginase-induced asparagine deprivation have been developed for acute lymphoblastic leukaemia. However, a tailored detection system for measuring restrictive amino acids in each tumour is c ...[more]

PMID: 26878238

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Project description:Cap1p, a transcription factor of the basic region-leucine zipper family, regulates oxidative stress response (OSR) in Candida albicans. Alteration of its C-terminal cysteine-rich domain (CRD) results in Cap1p nuclear retention and transcriptional activation. To better understand the function of Cap1p in C. albicans, we used genome-wide location profiling (ChIP-on-chip) to identify its transcriptional targets in vivo. A triple-hemagglutinin epitope was introduced at the C-terminus of wild-type Cap1p (Cap1p-HA3) or hyperactive Cap1p with an altered CRD (Cap1p-CSE-HA3). Location profiling using whole-genome oligonucleotide tiling microarrays identified 89 targets bound by Cap1p-HA3 or Cap1p-CSE-HA3 (binding ratio â?¥ 2-fold, P â?¤ 0.01). Strikingly, Cap1p binding was not only detected at the promoter region of its target genes but also at their 3'-end and within their open-reading frame, suggesting that Cap1p may associate with the transcriptional or the chromatin remodeling machinery to exert its activity. Overrepresented functional groups of the Cap1p targets (P â?¤ 0.02) included 11 genes involved in OSR (CAP1, GLR1, TRX1, SOD1, CAT1, others), 13 genes involved in response to drugs (PDR16, MDR1, FLU1, YCF1, FCR1, others), 4 genes involved in phospholipid transport (PDR16, GIT1, RTA2, orf19.932) and 3 genes involved in the regulation of nitrogen utilization (GST3, orf19.2693, orf19.3121), suggesting that Cap1p has other cellular functions in addition to OSR. Bioinformatic analyses of the bound sequences suggest that Cap1p recognizes the DNA motif 5'- MTKASTMA. Finally, transcriptome analyses showed that increased expression generally accompanies Cap1p binding at its targets, indicating that Cap1p functions as a transcriptional activator. Processing of raw data from 3 independent replicate samples for each Cap1 dataset was conducted using Tilescope (http://tilescope.gersteinlab.org:8080/mosaic/pipeline.html). Quantile normalization was applied to the data. The parameters used were as follows: window size of 400 bp, MaxGap of 60 bp and MinRun of 120 bp. The replicate data were combined and peak-finding (i.e. Cap1p-binding sites) was determined using the following criteria: pseudo-median signal threshold of â?¥ 2-fold and p-value cut-off of â?¤ 0.01.

Dataset Information

Restrictions in amino acid availability revealed by differential ribosome codon reading

Publications

Tumour-specific proline vulnerability uncovered by differential ribosome codon reading.

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