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PMID: 12975318 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cell cycle-dependent and cell cycle-independent control of transcription by the Drosophila E2F/RB pathway.

Genes & development ·Vol. 17 ·No. 18 ·2003-09-15 ·Pages 2308-20

Dimova DK, Stevaux O, Frolov MV, Dyson NJ

Abstract

To determine which E2F/RB-family members are functionally important at E2F-dependent promoters, we used RNA interference (RNAi) to selectively remove each component of the dE2F/dDP/RBF pathway, and we examined the genome-wide changes in gene expression that occur when each element is missing. The results reveal a remarkable division of labor between family members. Classic E2F targets, encoding functions needed for cell cycle progression, are expressed in cycling cells and are primarily dependent on dE2F1and RBF1 for regulation. Unexpectedly, there is a second program of dE2F/RBF-dependent transcription, in which dE2F2/RBF1or dE2F2/RBF2 complexes repress gene expression in actively proliferating cells. These new E2F target genes encode differentiation factors that are transcribed in developmentally regulated and gender-specific patterns and not in a cell cycle-regulated manner. We propose that dE2F/RBF complexes should not be viewed simply as a cell cycle regulator of transcription. Instead, dE2F/RBF-mediated repression is exerted on genes that encode an assortment of cellular functions, and these effects are reversed on sets of functionally related genes in particular developmental contexts. As a result, dE2F/RBF regulation is used to link gene expression with cell cycle progression at some targets while simultaneously providing stable repression at others.

MeSH Terms
Adaptor Proteins, Vesicular Transport/metabolism Animals Cell Cycle/physiology Drosophila/embryology,genetics Drosophila Proteins/metabolism E2F Transcription Factors Gene Expression Regulation, Developmental/physiology Oligonucleotide Array Sequence Analysis Promoter Regions, Genetic Transcription Factors/metabolism Transcription, Genetic/physiology
Chemicals
Adaptor Proteins, Vesicular Transport Drosophila Proteins E2F Transcription Factors E2f1 protein, Drosophila RB protein, Drosophila Transcription Factors
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Dimova Dessislava K
Massachusetts General Hospital Cancer Center, Charlestown, Massachusetts, 02129 USA.
Stevaux Olivier
Frolov Maxim V
Dyson Nicholas J
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Article Info
Journal
Genes & development
Abbr.
Genes Dev
ISSN
0890-9369
DOI
10.1101/gad.1116703
Published
2003-09-15
Pages
2308-20
Language
English
Region
United States
NLM ID
8711660
PMCID
PMC196467
Subset
IM
Grants
NCI NIH HHS · F32 CA093045 · United States
NIGMS NIH HHS · R01 GM053203 · United States
NCI NIH HHS · F32 CA93045 · United States
NIGMS NIH HHS · GM53203 · United States
External Links
PubMed source DOI: 10.1101/gad.1116703 PMC Full Text View journal details
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