Document Detail


The enhancer of trithorax and polycomb gene Caf1/p55 is essential for cell survival and patterning in Drosophila development.
MedLine Citation:
PMID:  21490066     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In vitro data suggest that the human RbAp46 and RbAp48 genes encode proteins involved in multiple chromatin remodeling complexes and are likely to play important roles in development and tumor suppression. However, to date, our understanding of the role of RbAp46/RbAp48 and its homologs in metazoan development and disease has been hampered by a lack of insect and mammalian mutant models, as well as redundancy due to multiple orthologs in most organisms studied. Here, we report the first mutations in the single Drosophila RbAp46/RbAp48 homolog Caf1, identified as strong suppressors of a senseless overexpression phenotype. Reduced levels of Caf1 expression result in flies with phenotypes reminiscent of Hox gene misregulation. Additionally, analysis of Caf1 mutant tissue suggests that Caf1 plays important roles in cell survival and segment identity, and loss of Caf1 is associated with a reduction in the Polycomb Repressive Complex 2 (PRC2)-specific histone methylation mark H3K27me3. Taken together, our results suggest suppression of senseless overexpression by mutations in Caf1 is mediated by participation of Caf1 in PRC2-mediated silencing. More importantly, our mutant phenotypes confirm that Caf1-mediated silencing is vital to Drosophila development. These studies underscore the importance of Caf1 and its mammalian homologs in development and disease.
Authors:
Aimée E Anderson; Umesh C Karandikar; Kathryn L Pepple; Zhihong Chen; Andreas Bergmann; Graeme Mardon
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-04-13
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  138     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-27     Completed Date:  2011-07-01     Revised Date:  2014-09-17    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  1957-66     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Animals, Genetically Modified
Apoptosis / genetics
Body Patterning / genetics
Cell Survival / genetics
Drosophila / genetics*,  growth & development*,  metabolism
Drosophila Proteins / genetics*
Epigenesis, Genetic
Eye / growth & development
Genes, Homeobox
Genes, Insect
Histone-Lysine N-Methyltransferase / genetics
Histones / genetics,  metabolism
Humans
Methylation
Models, Biological
Mutation
Nuclear Proteins / genetics
Phenotype
Polycomb Repressive Complex 1
Retinoblastoma-Binding Protein 4 / genetics*
Signal Transduction
Transcription Factors / genetics
Grant Support
ID/Acronym/Agency:
R01 EY011232/EY/NEI NIH HHS; R01 GM068016/GM/NIGMS NIH HHS; R01 GM068016/GM/NIGMS NIH HHS; R01 GM068016-10/GM/NIGMS NIH HHS; R01 GM074977/GM/NIGMS NIH HHS; R01 GM081543/GM/NIGMS NIH HHS; R01 GM081543/GM/NIGMS NIH HHS; R01 GM081543-05/GM/NIGMS NIH HHS; T32 CA009299/CA/NCI NIH HHS; T32 EY007102/EY/NEI NIH HHS
Chemical
Reg. No./Substance:
0/CAF1 protein, Drosophila; 0/Drosophila Proteins; 0/Histones; 0/Nuclear Proteins; 0/Polycomb protein, Drosophila; 0/Retinoblastoma-Binding Protein 4; 0/Transcription Factors; 0/senseless protein, Drosophila; EC 2.1.1.43/Histone-Lysine N-Methyltransferase; EC 2.1.1.43/PRC2 protein, Drosophila; EC 6.3.2.19/Polycomb Repressive Complex 1
Comments/Corrections

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