Biomedical subjects

Cynthia L Fisher

Publications and source records attributed to Cynthia L Fisher.

3 recordsLinked to original sources

PubMed2006

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 sex 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 PHD 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. Asxl1and Asxl2 are expressed as multiple transcripts, at varying levels, in adult tissues and in embryonic stem 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.

Amino Acid Sequence↗

PubMed2005

Maintenance of gene expression patterns.

In development, cells pass on established gene expression patterns to daughter cells over multiple rounds of cell division. The cellular memory of the gene expression state is termed maintenance, and the proteins required for this process are termed maintenance proteins. The best characterized are proteins of the Polycomb and trithorax Groups that are required for silencing and maintenance of activation of target loci, respectively. These proteins act through DNA elements termed maintenance elements. Here, we re-examine the genetics and molecular biology of maintenance proteins. We discuss molecular models for the maintenance of activation and silencing, and the establishment of epigenetic marks, and suggest that maintenance proteins may play a role in propagating the mark through DNA synthesis.

Animals↗

PubMed2003

A human homolog of Additional sex combs, ADDITIONAL SEX COMBS-LIKE 1, maps to chromosome 20q11.

The Additional sex combs (Asx) gene of Drosophila is an Enhancer of trithorax and Polycomb (ETP), and is required to maintain activation and silencing of homeotic loci. The molecular basis of this dual function is not understood. Here, we identify a human homolog of Asx, termed ADDITIONAL SEX COMBS-LIKE 1 (ASXL1). Overall, the amino acid sequence of ASXL1 has 21% identity and 41% similarity to Drosophila ASX. The ASXL1 protein contains a 118 amino acid conserved amino terminal region of unknown function that we term the ASX homology domain (ASXH) that contains two LXXLL consensus sequences for nuclear receptor binding. ASXL1 also contains a conserved C-terminal cysteine cluster that is a variant of the PHD domain. Three ASXL1 transcripts of differing size are detected, which are widely expressed in adult tissues. ASXL1 maps to chromosome 20q11, a region frequently amplified in human tumors. Interestingly, ASXL1 is overexpressed in cell lines derived from carcinomas.

Amino Acid Sequence↗