Missense mutations identified in PU.1. (A) The 36 missense mutations identified in 34 myeloid tumors and/or derived cell lines. The mRNA sequence is numbered from the first AUG of the open reading frame. Two synonymous changes (C → T at bp 700 and G → C at bp 702) found in tumors that also displayed an adjacent Arg235 missense mutation are not shown. (B) Point mutations affect conserved positions in the Ets domain. On the relevant portion of the mouse PU.1 Ets domain, the 6 residues in which mutations were found are indicated in bold, with an asterisk marking the 5 that reside at well-conserved positions, illustrated by the corresponding Ets sequences from human PU.1, mouse Ets1, zebrafish Fli1, and Drosophila Yan.³⁰  Boldfacing indicates nucleotides and amino acids affected by mutations. (C) Diagram showing the domains of the PU.1 protein (TAD denotes the transcription activation domain), the location of the mutations found, and the regions (including the β3-β4 region of the Ets domain³⁰ ) through which PU.1 engages other transcription factors.²