title: Wapl antagonizes cohesin binding and promotes Polycomb-group silencing in Drosophila.
abstract: 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.affiliation: Program in Genomics of Differentiation, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892,  USA.
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Cunningham
authors.forename: Maria
authors.initials: M
authors.lastname: Gause
authors.forename: Yuzhong
authors.initials: Y
authors.lastname: Cheng
authors.forename: Amanda
authors.initials: A
authors.lastname: Noyes
authors.forename: Dale
authors.initials: D
authors.lastname: Dorsett
authors.forename: James A
authors.initials: JA
authors.lastname: Kennison
authors.forename: Judith A
authors.initials: JA
authors.lastname: Kassis
mesh_terms: D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D018389:Codon, Nonsense; D004247:DNA / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D009154:Mutation; D010641:Phenotype; D063150:Polycomb Repressive Complex 1 / Q000235:genetics* / Q000378:metabolism; D059007:Polytene Chromosomes / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000097722:Cohesins
chemical_list: D002868:Chromosomal Proteins, Non-Histone; D018389:Codon, Nonsense; D004247:DNA; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D063150:Polycomb Repressive Complex 1; D014157:Transcription Factors; C063459:En protein, Drosophila; C066770:Pc protein, Drosophila; C541515:Pds5 protein, Drosophila; C554564:Wapl protein, Drosophila; C506513:cohesin protein complex, Drosophila; D000097722:Cohesins; C119839:nipped-B protein, Drosophila