Ch. 16 - Regulation of Gene Expression in Eukaryotes
Klug10th EditionEssentials of GeneticsISBN: 9780135588789
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TOC.tableOfContents
- Ch. 1 - Introduction to Genetics16
- Ch. 2 - Mitosis and Meiosis28
- Ch. 3 - Mendelian Genetics37
- Ch. 4 - Modification of Mendelian Ratios53
- Ch. 5 - Sex Determination and Sex Chromosomes32
- Ch. 6 - Chromosome Mutations: Variation in Number and Arrangement37
- Ch. 7 - Linkage and Chromosome Mapping in Eukaryotes36
- Ch. 8 - Genetic Analysis and Mapping in Bacteria and Bacteriophages24
- Ch. 9 - DNA Structure and Analysis38
- Ch. 10 - DNA Replication29
- Ch. 11 - Chromosome Structure and DNA Sequence Organization22
- Ch. 12 - The Genetic Code and Transcription36
- Ch. 13 - Translation and Proteins27
- Ch. 14 - Gene Mutation, DNA Repair, and Transposition34
- Ch. 15 - Regulation of Gene Expression in Bacteria22
- Ch. 16 - Regulation of Gene Expression in Eukaryotes37
- Ch. 17 - Recombinant DNA Technology27
- Ch. 18 - Genomics, Bioinformatics, and Proteomics30
- Ch. 19 - The Genetics of Cancer21
- Ch. 20 - Quantitative Genetics and Multifactorial Traits37
- Ch. 21 - Population and Evolutionary Genetics45
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Klug 10th EditionCh. 16 - Regulation of Gene Expression in EukaryotesProblema 29b
Klug 10th EditionCh. 16 - Regulation of Gene Expression in EukaryotesProblema 29bCapitolo 16, Problema 29b
Many viruses that infect eukaryotic cells express genes that alter the regulation of host gene expression to promote viral replication. For example, herpes simplex virus-1 (HSV-1) expresses a protein called ICP0, which is necessary for successful viral infection and replication within the host. Lutz et al. (2017. Viruses 9: 210) showed that ICP0 can act as a ubiquitin ligase and target the redundant transcriptional repressors ZEB1 and ZEB2, which leads to upregulation of the miR-183 cluster (a set of three miRNAs transcribed from the same locus).
How may ICP0 expression in a host cell lead to upregulation of the miR-183 cluster?
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Understand the role of ICP0: ICP0 is a viral protein that functions as a ubiquitin ligase, meaning it can tag specific host proteins with ubiquitin to mark them for degradation by the proteasome.
Identify the target proteins: ICP0 targets the transcriptional repressors ZEB1 and ZEB2. These repressors normally bind to the promoter region of the miR-183 cluster and inhibit its transcription.
Explain the effect of ubiquitination: When ICP0 ubiquitinates ZEB1 and ZEB2, it leads to their degradation, reducing their levels in the host cell.
Connect the degradation to gene expression: With fewer ZEB1 and ZEB2 repressors available, the repression on the miR-183 cluster is lifted, allowing increased transcription of the miR-183 cluster genes.
Summarize the outcome: Therefore, ICP0 expression indirectly causes upregulation of the miR-183 cluster by removing the transcriptional repression mediated by ZEB1 and ZEB2.
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Ubiquitin-Mediated Protein Degradation
Ubiquitin ligases tag specific proteins with ubiquitin molecules, marking them for degradation by the proteasome. This process regulates protein levels and activity within the cell. ICP0 acts as a ubiquitin ligase, targeting repressors like ZEB1 and ZEB2 for degradation, thereby altering gene expression.
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05:05
Proteins
Transcriptional Repressors and Gene Regulation
Transcriptional repressors such as ZEB1 and ZEB2 bind to DNA and inhibit the transcription of target genes. By degrading these repressors, the repression is lifted, allowing increased transcription of genes or gene clusters, like the miR-183 cluster, which are otherwise kept at low expression levels.
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Percorso guidato
09:22Review of Regulation
MicroRNA (miRNA) Clusters and Their Regulation
miRNA clusters are groups of microRNAs transcribed together from a single genomic locus, often regulating gene expression post-transcriptionally. The miR-183 cluster consists of three miRNAs whose expression can be controlled by transcription factors and repressors. Upregulation of this cluster can influence cellular pathways important for viral replication.
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06:38Regulation
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