A SINGLE AMINO-ACID SUBSTITUTION IN THE ETS DOMAIN ALTERS CORE DNA-BINDING SPECIFICITY OF ETS1 TO THAT OF THE RELATED TRANSCRIPTION FACTORSELF1 AND E74

Ets proteins form a family of sequence specific DNA binding proteins w hich bind DNA through a 85 aminoacids conserved domain, the Ets domain , whose sequence is unrelated to any other characterized DNA binding d omain. Unlike all other known Ets proteins, which bind specific DNA se quences centered over either GGAA or GGAT core motifs, E74 and Elf1 se lectively bind to GGAA corecontaining sites. Elf1 and E74 differ from other Ets proteins in three residues located in an otherwise highly co nserved region of the Ets domain, referred to as conserved region III (CRIII). We show that a restricted selectivity for GGAA core-containin g sites could be conferred to Ets1 upon changing a single lysine resid ue within CRIII to the threonine found in Elf1 and E74 at this positio n. Conversely, the reciprocal mutation in Elf1 confers to this protein the ability to bind to GGAT core containing EBS. This, together with the fact that mutation of two invariant arginine residues in CRIII abo lishes DNA binding, indicates that CRIII plays a key role in Ets domai n recognition of the GGAA/T core motif and lead us to discuss a model of Ets proteins - core motif interaction.