Document Detail


In vivo regulation of E2F1 by Polycomb group genes in Drosophila.
MedLine Citation:
PMID:  23275887     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The E2F transcription factors are important regulators of the cell cycle whose function is commonly misregulated in cancer. To identify novel regulators of E2F1 activity in vivo, we used Drosophila to conduct genetic screens. For this, we generated transgenic lines that allow the tissue-specific depletion of dE2F1 by RNAi. Expression of these transgenes using Gal4 drivers in the eyes and wings generated reliable and modifiable phenotypes. We then conducted genetic screens testing the capacity of Exelixis deficiencies to modify these E2F1-RNAi phenotypes. From these screens, we identified mutant alleles of Suppressor of zeste 2 [Su(z)2] and multiple Polycomb group genes as strong suppressors of the E2F1-RNA interference phenotypes. In validation of our genetic data, we find that depleting Su(z)2 in cultured Drosophila cells restores the cell-proliferation defects caused by reduction of dE2F1 by elevating the level of dE2f1. Furthermore, analyses of methylation status of histone H3 lysine 27 (H3K27me) from the published modENCODE data sets suggest that the genomic regions harboring dE2f1 gene and certain dE2f1 target genes display H3K27me during development and in several Drosophila cell lines. These in vivo observations suggest that the Polycomb group may regulate cell proliferation by repressing the transcription of dE2f1 and certain dE2F1 target genes. This mechanism may play an important role in coordinating cellular differentiation and proliferation during Drosophila development.
Authors:
Jun-Yuan Ji; Wayne O Miles; Michael Korenjak; Yani Zheng; Nicholas J Dyson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-01
Journal Detail:
Title:  G3 (Bethesda, Md.)     Volume:  2     ISSN:  2160-1836     ISO Abbreviation:  G3 (Bethesda)     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-31     Completed Date:  2013-06-03     Revised Date:  2013-07-11    
Medline Journal Info:
Nlm Unique ID:  101566598     Medline TA:  G3 (Bethesda)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1651-60     Citation Subset:  IM    
Affiliation:
Department of Molecular and Cellular Medicine, College of Medicine, Texas A&M Health Science Center, College Station, Texas 77843-1114, USA. ji@medicine.tamhsc.edu
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MeSH Terms
Descriptor/Qualifier:
Alleles
Animals
Animals, Genetically Modified / genetics
DNA-Binding Proteins / genetics*,  metabolism
Drosophila / genetics*
Drosophila Proteins / antagonists & inhibitors,  genetics*,  metabolism
E2F1 Transcription Factor / antagonists & inhibitors,  genetics*,  metabolism
Histones / metabolism
Methylation
Phenotype
Polycomb-Group Proteins / genetics*,  metabolism
RNA Interference
Grant Support
ID/Acronym/Agency:
R01GM053203/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/DNA-Binding Proteins; 0/Drosophila Proteins; 0/E2F1 Transcription Factor; 0/Histones; 0/Polycomb-Group Proteins; 0/Su(z)2 protein, Drosophila
Comments/Corrections

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