Home LiteratureArticle Details
PMID: 15456884 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

p55, the Drosophila ortholog of RbAp46/RbAp48, is required for the repression of dE2F2/RBF-regulated genes.

Molecular and cellular biology ·Vol. 24 ·No. 20 ·2004-10-00 ·Pages 9124-36

Taylor-Harding B, Binné UK, Korenjak M, Brehm A, Dyson NJ

Abstract

Many proteins have been proposed to be involved in retinoblastoma protein (pRB)-mediated repression, but it is largely uncertain which cofactors are essential for pRB to repress endogenous E2F-regulated promoters. Here we have taken advantage of the stream-lined Drosophila dE2F/RBF pathway, which has only two E2Fs (dE2F1 and dE2F2), and two pRB family members (RBF1 and RBF2). With RNA interference (RNAi), we depleted potential corepressors and looked for the elevated expression of groups of E2F target genes that are known to be directly regulated by RBF1 and RBF2. Previous studies have implicated histone deacetylase (HDAC) and SWI/SNF chromatin-modifying complexes in pRB-mediated repression. However, our results fail to support the idea that the SWI/SNF proteins are required for RBF-mediated repression and suggest that a requirement for HDAC activities is likely to be limited to a subset of targets. We found that the chromatin assembly factor p55/dCAF-1 is essential for the repression of dE2F2-regulated targets. The removal of p55 deregulated the expression of E2F targets that are normally repressed by dE2F2/RBF1 and dE2F2/RBF2 complexes in a cell cycle-independent manner but had no effect on the expression of E2F targets that are normally coupled with cell proliferation. The results indicate that the mechanisms of RBF regulation at these two types of E2F targets are different and suggest that p55, and perhaps p55's mammalian orthologs RbAp46 and RbAp48, have a conserved function in repression by pRB-related proteins.

MeSH Terms
Animals Carrier Proteins/metabolism Cells, Cultured Chromosomal Proteins, Non-Histone/genetics,metabolism Drosophila Proteins/genetics,metabolism Drosophila melanogaster/genetics,physiology E2F2 Transcription Factor Gene Expression Regulation Histone Deacetylase Inhibitors Histone Deacetylases/metabolism Humans Molecular Chaperones/genetics,metabolism Nuclear Proteins/metabolism Promoter Regions, Genetic Protein Binding RNA Interference Repressor Proteins/genetics,metabolism Retinoblastoma Protein/genetics,metabolism Retinoblastoma-Binding Protein 4 Retinoblastoma-Binding Protein 7 Transcription Factors/genetics,metabolism
Chemicals
Caf1-55 protein, Drosophila Carrier Proteins Chromosomal Proteins, Non-Histone Drosophila Proteins E2F2 Transcription Factor E2f2 protein, Drosophila Histone Deacetylase Inhibitors Molecular Chaperones Nuclear Proteins RBBP7 protein, human RBF2 protein, Drosophila Rbf protein, Drosophila Repressor Proteins Retinoblastoma Protein Retinoblastoma-Binding Protein 4 Retinoblastoma-Binding Protein 7 Transcription Factors Histone Deacetylases
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Taylor-Harding Barbie
Massachusetts General Hospital, Center for Cancer Research, Building 149, 13th St., Charlestown, MA 02129, USA.
Binné Ulrich K
Korenjak Michael
Brehm Alexander
Dyson Nicholas J
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.20.9124-9136.2004
Published
2004-10-00
Pages
9124-36
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC517895
Subset
IM
Grants
NIGMS NIH HHS · R01 GM053203 · United States
NIGMS NIH HHS · GM53203 · United States
External Links
PubMed source DOI: 10.1128/MCB.24.20.9124-9136.2004 PMC Full Text View journal details
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