期刊
DEVELOPMENTAL BIOLOGY
卷 337, 期 1, 页码 9-15出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ydbio.2009.10.004
关键词
Hox; Antero-posterior axis; Epigenetic
资金
- Canadian Institutes of Health Research
- N.I.H (USA)
- Terry Fox Foundation [R01-CA-0078815]
- Leukemia and Lymphoma Society of America
- Medical Research Council of Canada
- CIHR New Investigator
- NATIONAL CANCER INSTITUTE [R01CA078815, R01CA092251] Funding Source: NIH RePORTER
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. (C) 2009 Elsevier Inc. All rights reserved.
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