دورية أكاديمية
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Linking yeast Gcn5p catalytic function and gene regulation using a quantitative, graded dominant mutant approach.

التفاصيل البيبلوغرافية
العنوان: Linking yeast Gcn5p catalytic function and gene regulation using a quantitative, graded dominant mutant approach.
المؤلفون: Lanza AM; Department of Chemical Engineering, The University of Texas at Austin, Austin, Texas, USA., Blazeck JJ, Crook NC, Alper HS
المصدر: PloS one [PLoS One] 2012; Vol. 7 (4), pp. e36193. Date of Electronic Publication: 2012 Apr 27.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Public Library of Science Country of Publication: United States NLM ID: 101285081 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1932-6203 (Electronic) Linking ISSN: 19326203 NLM ISO Abbreviation: PLoS One Subsets: MEDLINE
أسماء مطبوعة: Original Publication: San Francisco, CA : Public Library of Science
مواضيع طبية MeSH: Biocatalysis* , Mutation* , Systems Biology*, Gene Expression Regulation, Fungal/*genetics , Histone Acetyltransferases/*metabolism , Saccharomyces cerevisiae/*genetics , Saccharomyces cerevisiae/*metabolism , Saccharomyces cerevisiae Proteins/*metabolism, Acetylation ; Histones/metabolism ; Phenotype ; Saccharomyces cerevisiae/cytology ; Transcriptome/genetics
مستخلص: Establishing causative links between protein functional domains and global gene regulation is critical for advancements in genetics, biotechnology, disease treatment, and systems biology. This task is challenging for multifunctional proteins when relying on traditional approaches such as gene deletions since they remove all domains simultaneously. Here, we describe a novel approach to extract quantitative, causative links by modulating the expression of a dominant mutant allele to create a function-specific competitive inhibition. Using the yeast histone acetyltransferase Gcn5p as a case study, we demonstrate the utility of this approach and (1) find evidence that Gcn5p is more involved in cell-wide gene repression, instead of the accepted gene activation associated with HATs, (2) identify previously unknown gene targets and interactions for Gcn5p-based acetylation, (3) quantify the strength of some Gcn5p-DNA associations, (4) demonstrate that this approach can be used to correctly identify canonical chromatin modifications, (5) establish the role of acetyltransferase activity on synthetic lethal interactions, and (6) identify new functional classes of genes regulated by Gcn5p acetyltransferase activity--all six of these major conclusions were unattainable by using standard gene knockout studies alone. We recommend that a graded dominant mutant approach be utilized in conjunction with a traditional knockout to study multifunctional proteins and generate higher-resolution data that more accurately probes protein domain function and influence.
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المشرفين على المادة: 0 (Histones)
0 (Saccharomyces cerevisiae Proteins)
EC 2.3.1.48 (GCN5 protein, S cerevisiae)
EC 2.3.1.48 (Histone Acetyltransferases)
تواريخ الأحداث: Date Created: 20120505 Date Completed: 20120904 Latest Revision: 20211021
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC3338614
DOI: 10.1371/journal.pone.0036193
PMID: 22558379
قاعدة البيانات: MEDLINE
الوصف
تدمد:1932-6203
DOI:10.1371/journal.pone.0036193