Additional sex combs-like 1 belongs to the enhancer of trithorax and polycomb group and genetically interacts with Cbx2 in mice

C. L. Fisher, I. Lee, S. Bloyer, S. Bozza, J. Chevalier, A. Dahl, C. Bodner, C. D. Helgason, J. L. Hess, R. K. Humphries, H. W. Brock

Research output: Contribution to journalArticle

50 Scopus citations

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 Asxl1tm1Bc 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 Asxl1tm1Bc 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.

Original languageEnglish (US)
Pages (from-to)9-15
Number of pages7
JournalDevelopmental Biology
Volume337
Issue number1
DOIs
StatePublished - Jan 1 2010
Externally publishedYes

Keywords

  • Antero-posterior axis
  • Epigenetic
  • Hox

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology

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    Fisher, C. L., Lee, I., Bloyer, S., Bozza, S., Chevalier, J., Dahl, A., Bodner, C., Helgason, C. D., Hess, J. L., Humphries, R. K., & Brock, H. W. (2010). Additional sex combs-like 1 belongs to the enhancer of trithorax and polycomb group and genetically interacts with Cbx2 in mice. Developmental Biology, 337(1), 9-15. https://doi.org/10.1016/j.ydbio.2009.10.004