Systematic and functional genomics of coding and non-coding transcription during gene expression regulation in yeast

酵母基因表达调控过程中编码和非编码转录的系统和功能基因组学

• 批准号: 344650877
• 负责人: Professor Dr. Michael Knop
• 金额: --
• 依托单位: Zentrum für Molekulare Biologie (ZMBH)
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2017
• 资助国家: 德国
• 起止时间: 2016-12-31 至 2020-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/344650877?language=en
• 关键词: Systematic; functional; genomics; coding; non

Cellular protein homeostasis ensures that the optimal amount of each protein is available at its site of action within an organism. This homeostasis is monitored by a series of regulatory systems - from control of gene expression and mRNA translation to protein removal via degradation pathways. Together they ensure the ideal amount of each protein in any given situation. It has become evident that the classical model of promoter-mediated gene regulation alone cannot fully explain gene expression. Rather, a number of other factors, such as transcription of overlapping non-coding RNAs, chromatin structure and genomic location, also play important roles in gene regulation. The aim of this project is to investigate the regulation of single genes comprehensively in order to quantify the contribution of each of these factors. To reach this goal, we will apply two complementary methods based on high-throughput genetics and CRISPR/Cas9 mediated genome editing. We will use baker's yeast as a model organism to explore a large number of genes, coding sequences and non-coding transcripts in the context of cellular fitness. The project will be carried out within a well-established collaboration between a genome biology / bioinformatics oriented work group at EMBL and a cell biology group at the ZMBH. The experiments we will perform aim at exploring the basic principles of gene regulation using quantitative methods.

细胞蛋白稳态确保在生物体内的作用部位可用每种蛋白质的最佳量。通过一系列调节系统来监测这种稳态 - 从控制基因表达和mRNA翻译到通过降解途径去除蛋白质。它们共同确保在任何给定情况下每种蛋白质的理想量。显而易见的是，仅启动子介导的基因调节的经典模型无法完全解释基因表达。相反，许多其他因素，例如重叠的非编码RNA，染色质结构和基因组位置的转录，在基因调节中也起着重要作用。该项目的目的是全面研究单个基因的调节，以量化每个因素的贡献。为了实现这一目标，我们将采用两种基于高通量遗传学和CRISPR/CAS9介导的基因组编辑的补充方法。在细胞适应性的背景下，我们将使用贝克的酵母作为模型生物来探索大量基因，编码序列和非编码转录本。该项目将在EMBL的基因组生物学 /生物信息学工作组与ZMBH的细胞生物学组之间进行良好的合作。我们将执行的实验旨在使用定量方法探索基因调节的基本原理。

项目成果

Chromatin-sensitive cryptic promoters putatively drive expression of alternative protein isoforms in yeast

染色质敏感的隐性启动子可能驱动酵母中替代蛋白质亚型的表达

• DOI: 10.1101/gr.243378.118
• 发表时间: 2019-11
• 期刊: Genome Research
• 影响因子: 7
• 作者: Wu Wei;Bianca P. Hennig;Jingwen Wang;Yujie Zhang;Ilaria Piazza;Yerma Pareja Sanchez;Christophe D. Chabbert;Sophie H. Adjalley;Lars M. Steinmetz;Vicent Pelechano
• 通讯作者: Vicent Pelechano

Rpb4 and Puf3 imprint and post-transcriptionally control the stability of a common set of mRNAs in yeast

• DOI: 10.1080/15476286.2020.1839229
• 发表时间: 2020-11-02
• 期刊: RNA BIOLOGY
• 影响因子: 4.1
• 作者: Garrido-Godino, A. I.;Gupta, I.;Navarro, F.
• 通讯作者: Navarro, F.

Gene dosage screens in yeast reveal core signalling pathways controlling heat adaptation

酵母中的基因剂量筛选揭示了控制热适应的核心信号通路

• DOI: 10.1101/2020.08.26.267674
• 发表时间: 2020
• 期刊: bioRxiv
• 作者: A. Johansson;J.D. Smith;L. Parts;L.M. Steinmetz
• 通讯作者: L.M. Steinmetz