Distributed transcription activity in DLX proteins defies conventional mapping of a transcription activation domain

The DNA binding domains of transcription factors are structurally well-defined and their presence in novel genome sequence can be reliably detected via sequence homology. In contrast, regions of transcription factors that stimulate or repress mRNA synthesis by RNA polymerase II are more enigmatic and difficult to identify with bioinformatic tools. Experimental discovery of transactivation (or repression) domains typically makes use of a reporter gene transcription assay in one or more cell types and the progressive removal of protein sequence from the transcription factor under study. By and large, this reveals one or more minimal subdomains that are required for most of the transcription activity for the wild type protein. In applying this approach to the experimental identification of minimal transactivation domains of the chicken DLX5 and DLX6 paralogues, we find no obvious subdomain organization but, instead, show redundant transactivation activity that is distributed throughout each protein. We also reveal that DLX domains can cooperate in trans in homo- or heterotypic reactions with DLX domains that are DNA-bound via the homeodomain.