title: Additional sex combs-like 1 belongs to the enhancer of trithorax and polycomb group and genetically interacts with Cbx2 in mice.
abstract: The Additional sex combs (Asx) gene of Drosophila behaves genetically as an enhancer of trithorax and polycomb (ETP) in displaying bidirectional homeotic phenotypes, suggesting that is required for maintenance of both activation and silencing of Hox genes. There are three murine homologs of Asx called Additional sex combs-like1, 2, and 3. Asxl1 is required for normal adult hematopoiesis; however, its embryonic function is unknown. We used a targeted mouse mutant line Asxl1(tm1Bc) to determine if Asxl1 is required to silence and activate Hox genes in mice during axial patterning. The mutant embryos exhibit simultaneous anterior and posterior transformations of the axial skeleton, consistent with a role for Asxl1 in activation and silencing of Hox genes. Transformations of the axial skeleton are enhanced in compound mutant embryos for the polycomb group gene M33/Cbx2. Hoxa4, Hoxa7, and Hoxc8 are derepressed in Asxl1(tm1Bc) mutants in the antero-posterior axis, but Hoxc8 expression is reduced in the brain of mutants, consistent with Asxl1 being required both for activation and repression of Hox genes. We discuss the genetic and molecular definition of ETPs, and suggest that the function of Asxl1 depends on its cellular context.
authors.affiliation: Department of Zoology, University of British Columbia, 2350 Health Sciences Mall, Vancouver, British Columbia V6T1Z3, Canada.
authors.forename: C L
authors.initials: CL
authors.lastname: Fisher
authors.forename: I
authors.initials: I
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Bloyer
authors.forename: S
authors.initials: S
authors.lastname: Bozza
authors.forename: J
authors.initials: J
authors.lastname: Chevalier
authors.forename: A
authors.initials: A
authors.lastname: Dahl
authors.forename: C
authors.initials: C
authors.lastname: Bodner
authors.forename: C D
authors.initials: CD
authors.lastname: Helgason
authors.forename: J L
authors.initials: JL
authors.lastname: Hess
authors.forename: R K
authors.initials: RK
authors.lastname: Humphries
authors.forename: H W
authors.initials: HW
authors.lastname: Brock
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001842:Bone and Bones / Q000002:abnormalities*; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D018398:Homeodomain Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D010641:Phenotype; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011247:Pregnancy; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D013131:Spine / Q000002:abnormalities; D014157:Transcription Factors
chemical_list: C510915:Asxl1 protein, mouse; C570426:Cbx2 protein, mouse; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; C484111:Hoxa4 protein, mouse; D063146:Polycomb-Group Proteins; D012097:Repressor Proteins; D014157:Transcription Factors; D063150:Polycomb Repressive Complex 1