Ontology highlight
ABSTRACT:
PROVIDER: PRJNA718744 | ENA |
REPOSITORIES: ENA
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Project description:High-level production of pharmaceutical proteins in industrial microorganism is often limited due to the increased cellular stress from misfolded proteins or protein aggregates. Here, we explore the feasibility of applying a yeast Alzheimer’s disease (AD) model with accumulation of amyloid-β peptides (Aβ42), which presents similar phenotypes of cellular stress. We utilize the suppressors of Aβ42 cytotoxicity as potential metabolic engineering targets to improve industrial protein production. The transcriptomics analyses provide new insights towards developing synthetic yeast cell factories for biosynthesis of valuable pharmaceutical proteins.
2022-05-16 | GSE185570 | GEO
Project description:Genomic surveys of yeast hybrid species isolated from the wild and from human-related environment, aimed at the reconstruction of the natural evolution of Saccharomyces spp. evolution
2016-04-30 | E-SYBR-11 | biostudies-arrayexpress
Project description:We developed an artificial genome evolution system, which we termed ‘TAQing’, by introducing multiple genomic DNA double-strand breaks using a heat-activatable endonuclease in mitotic yeast. The heat-activated endonuclease, TaqI, induced random DSBs, which resulted in diverse types of chromosomal rearrangements including translocations. Array comparative genomic hybridization (aCGH) analysis was performed with cell-fused Saccharomyces cerevisiae strains induced genome evolution by TAQing system. Some of copy number variations (CNVs) induced by massive genome rearrangements were detected in the TAQed yeast strains.
2018-05-02 | GSE90025 | GEO
Project description:In this study, we used a yeast Alzheimer’s disease model in which amyloid-β peptides (Aβ42) accumulate and induce stress-related phenotypes similar to overexpression of recombinant proteins. We validated that suppressors of Aβ42 cytotoxicity could reduce cell stress and improve recombinant protein production. Omics analyses and reverse metabolic engineering reveal potential regulatory hubs in cellular metabolism and protein synthesis, which may provide guidelines for engineering other cell factories for efficient protein production.
2022-05-12 | PXD030111 | Pride
Project description:Transcription steps are marked by different modifications of the C-terminal domain of RNA polymerase II (RNAPII). Phosphorylation of Ser5 and Ser7 by cyclin-dependent kinase 7 (CDK7) as part of TFIIH marks initiation, whereas phosphorylation of Ser2 by CDK9 marks elongation. These processes are thought to take place in localized transcription foci in the nucleus, known as M-bM-^@M-^XM-bM-^@M-^Xtranscription factories,M-bM-^@M-^YM-bM-^@M-^Y but it has been argued that the observed clusters/foci are mere fixation or labeling artifacts. We show that transcription factories exist in living cells as distinct foci by live-imaging fluorescently labeled CDK9, a kinase known to associate with active RNAPII. These foci were observed in different cell types derived from CDK9-mCherry knock-in mice. We show that these foci are very stable while highly dynamic in exchanging CDK9. Chromatin immunoprecipitation (ChIP) coupled with deep sequencing (ChIP-seq) data show that the genome-wide binding sites of CDK9 and initiating RNAPII overlap on transcribed genes. Immunostaining shows that CDK9- mCherry foci colocalize with RNAPII-Ser5P, much less with RNAPII-Ser2P, and not with CDK12 (a kinase reported to be involved in the Ser2 phosphorylation) or with splicing factor SC35. In conclusion, transcription factories exist in living cells, and initiation and elongation of transcripts takes place in different nuclear compartments. Examination of genome occupancy of CDK9 and RNAPII that was performed by ChIP-seq in the MEL cell line as described (Soler et al. 2010, 2011) using CDK9 C20 antibody (Santa Cruz Biotechnology, C20, sc-484) and RNA Pol II antibody (Santa Cruz Biotechnology, N20, sc899),
2013-05-13 | E-GEOD-46849 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE24770: Heterochronic Evolution Reveals Modular Timing Changes in Budding Yeast Transcriptomes (Mutation Accumulation Lines) GSE24771: Heterochronic Evolution Reveals Modular Timing Changes in Budding Yeast Transcriptomes (Natural Strain Timecourse) Refer to individual Series
2010-10-19 | E-GEOD-24772 | biostudies-arrayexpress
Project description:Non-coding sense and antisense germline transcription within the immunoglobulin heavy chain locus precedes V(D)J recombination and has been proposed to be associated with Igh locus accessibility, although its precise role remains elusive. However, no global analysis of germline transcription throughout the Igh locus has been done. Therefore, we performed directional RNAseq, demonstrating the locations and extent of both sense and antisense transcription throughout the Igh locus. Surprisingly, the majority of antisense transcripts are localized around two PAIR elements in the distal IghV region. Importantly, long-distance loops measured by 3C are observed between these two active PAIR promoters and EM-NM-<, the start site of IM-NM-< germline transcription, in a lineage- and stage-specific manner, even though this antisense transcription is EM-NM-<-independent. YY1-/- pro-B cells are greatly impaired in distal VH gene rearrangement and Igh locus compaction, and we demonstrate that YY1 deficiency greatly reduces antisense transcription and PAIR-EM-NM-< interactions. ChIP-seq shows high level YY1 binding only at EM-NM-<, but low levels near some antisense promoters. PAIR-EM-NM-< interactions are not disrupted by DRB, which blocks transcription elongation without disrupting transcription factories once they are established, but the looping is reduced after heat shock treatment, which disrupts transcription factories. We propose that transcription-mediated interactions, most likely at transcription factories, initially compact the Igh locus, bringing distal VH genes close to the DJH rearrangement, which is adjacent to EM-NM-<. Therefore, we hypothesize that one key role of non-coding germline transcription is to facilitate locus compaction, allowing distal VH genes to undergo efficient rearrangement. ChIP Seq YY1 vs. input control
2012-10-18 | E-GEOD-40822 | biostudies-arrayexpress
Project description:The construction of powerful cell factories requires extensive remodelling of microbial genomes, entailing many rounds of transformations to perform the large number of desired gene modifications. However, increasing the number of genetic interventions inevitably increases the occurrence of unwanted mutations and effects. Using glycolysis as paradigm, a previous study developed a Saccharomyces cerevisiae strain in which the glycolytic genes, relocalized to a single locus, can be easily swapped by any new design, thereby enabling fast and easy remodelling of the entire pathway. After 27 genetic modifications performed in 43 transformation rounds, the Switchable Yeast Glycolysis (SwYG) strain grew ca. 20% slower than its ancestor with native glycolysis design. Exploring the cause of this slower growth rate, the present study reflects on the genetic and analytical challenges encountered by extensive strain construction programs and provides design guidelines for integration of large constructs in the yeast genome.
2021-12-06 | GSE190122 | GEO