Document Detail


Wapl antagonizes cohesin binding and promotes Polycomb-group silencing in Drosophila.
MedLine Citation:
PMID:  23034634     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Wapl protein regulates binding of the cohesin complex to chromosomes during interphase and helps remove cohesin from chromosomes at mitosis. We isolated a dominant mutation in wapl (wapl(AG)) in a screen for mutations that counteract silencing mediated by an engrailed Polycomb-group response element. wapl(AG) hemizygotes die as pharate adults and have an extra sex combs phenotype characteristic of males with mutations in Polycomb-group (PcG) genes. The wapl gene encodes two proteins, a long form and a short form. wapl(AG) introduces a stop codon at amino acid 271 of the long form and produces a truncated protein. The expression of a transgene encoding the truncated Wapl-AG protein causes an extra-sex-comb phenotype similar to that seen in the wapl(AG) mutant. Mutations in the cohesin-associated genes Nipped-B and pds5 suppress and enhance wapl(AG) phenotypes, respectively. A Pds5-Wapl complex (releasin) removes cohesin from DNA, while Nipped-B loads cohesin. This suggests that Wapl-AG might exert its effects through changes in cohesin binding. Consistent with this model, Wapl-AG was found to increase the stability of cohesin binding to polytene chromosomes. Our data suggest that increasing cohesin stability interferes with PcG silencing at genes that are co-regulated by cohesin and PcG proteins.
Authors:
Melissa D Cunningham; Maria Gause; Yuzhong Cheng; Amanda Noyes; Dale Dorsett; James A Kennison; Judith A Kassis
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural     Date:  2012-10-03
Journal Detail:
Title:  Development (Cambridge, England)     Volume:  139     ISSN:  1477-9129     ISO Abbreviation:  Development     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-10-24     Completed Date:  2013-01-14     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  8701744     Medline TA:  Development     Country:  England    
Other Details:
Languages:  eng     Pagination:  4172-9     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Chromosomal Proteins, Non-Histone / genetics,  metabolism*
Codon, Nonsense
DNA / metabolism
DNA-Binding Proteins / genetics,  metabolism
Drosophila / genetics*,  metabolism*
Drosophila Proteins / genetics*,  metabolism*
Gene Expression Regulation, Developmental
Gene Silencing*
Homeodomain Proteins / genetics,  metabolism
Male
Mutation
Phenotype
Polycomb Repressive Complex 1 / genetics*,  metabolism
Polytene Chromosomes / metabolism*
Transcription Factors / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
R01 GM055683/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Chromosomal Proteins, Non-Histone; 0/Codon, Nonsense; 0/DNA-Binding Proteins; 0/Drosophila Proteins; 0/Homeodomain Proteins; 0/Pds5 protein, Drosophila; 0/Polycomb protein, Drosophila; 0/Transcription Factors; 0/Wapl protein, Drosophila; 0/cohesin protein complex, Drosophila; 0/engrail protein, Drosophila; 0/nipped-B protein, Drosophila; 9007-49-2/DNA; EC 6.3.2.19/Polycomb Repressive Complex 1
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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