Characterization of Asxl1, a murine homolog of Additional sex combs, and analysis of the Asx-like gene family

The Additional sex combs (Asx) gene of Drosophila is required to maintain homeotic gene activation and silencing. Here we characterize the three murine homologs of Asx: Additional saex combs-like (Asxl1, Asxl2, and Asxl3) and identify conserved sequence features. The predicted amino acid sequence of Asxl1 has 16% identity and 40% similarity to Drosophila Asx, and 74% identity and 81% similarity to human ASXL1. Murine Asxl1 contains two regions highly conserved with Drosophila Asx: 1) a conserved amino terminal region of unknown function, termed the ASX homology domain (ASXH) which contains two nuclear receptor (NR) co-regulator binding motifs; and 2) a conserved C-terminal PHI) domain. The mammalian Asx-like predicted proteins possess additional conserved sequence features of unknown function not present in Drosophila Asx, including three more NR co-regulator binding motifs. Asx1 and Asxl2 are expressed as multiple transcripts, at varying levels, in adult tissues and in embryonic stein cells analyzed by Northern blot, and exhibit similar expression patterns suggesting they may be co-regulated. Whole mount RNA in situ hybridization revealed that Asxl1 is also expressed in 10.5-11.0 dpc mouse embryos. (C) 2005 Elsevier B.V. All rights reserved.