International Mammalian Genome Society

The 15th International Mouse Genome Conference (2001)


Dr Isabel Hanson
Dept. of Medical Sciences
University of Edinburgh
Molecular Medicine Centre
Western General Hospital
Crewe Road
Edinburgh EH4 2XU

Co-Authors: Brown AG
Institutions: Medical Genetics Section, University of Edinburgh, Molecular Medicine Centre, Western General Hospital,

Members of the SIX gene family are involved in a variety of developmental processes in vertebrates and invertebrates. All SIX genes encode two highly conserved motifs, a homeodomain that mediates DNA binding, and a SIX domain that mediates protein-protein interactions. With the near completion of various genome projects, it is now clear that Drosophila has three SIX genes (sine oculis, optix and D-Six4) while mammals have six (SIX1-6). Phylogenetic analysis of Drosophila and mammalian amino acid sequences shows that the proteins fall into three clear subgroups. An intriguing feature of the mammalian SIX genes is their genomic organisation; five of the six genes are clustered. We review the detailed organisation of the human genes, as recently revealed by the Human Genome Sequencing Project. Despite extensive amino acid homology within the SIX-domain, SIX proteins differ dramatically in their interactions with transcriptional co-factors encoded by the EYA gene family. We report work in progress which shows that while SIX1 interacts strongly with EYA2 and EYA4 in a yeast two-hybrid assay, SIX3 interacts with neither. This implies that there are clear functional differences between the subgroups of SIX proteins.

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