THE HOX11 GENE ENCODES A DNA-BINDING NUCLEAR TRANSCRIPTION FACTOR BELONGING TO A DISTINCT FAMILY OF HOMEOBOX GENES

A translocation involving human chromosome 10, band q24, in a subset o f T-cell acute leukemias disrupts a region surrounding the putative on cogene HOX11, which encodes a protein with a homeodomain. The HOX11 pr otein binds to a specific DNA sequence, it localizes to the cell nucle us, and it transactivates transcription of a reporter gene linked to a cis-regulatory element, suggesting that HOX11 functions in vivo as a positive transcription activator. PCR analysis shows that the HOX11 ho meodomain is a member of a distinct class of homeodomains, representat ives of which occur in murine and Drosophila genomes. These all contai n a threonine residue in place of the more common isoleucine or valine in helix 3 of the homeodomain. HOX11 therefore appears to belong to a family of DNA-binding transactivators of transcription.