A potential role for Pu.2 in erythroid differentiation, as described by Mak et al. PU.1 is a master regulator of myeloid differentiation (top). KLF1 and KLF3, respectively, activate and repress an alternative promoter included in an ORR1A0 LTR located in the second intron of Pu.1. KLF3-mediated suppression of this LTR is the norm in wild-type fetal liver cells, permitting canonical PU.1 expression and myeloid differentiation. In the absence of KLF3, Mak et al. found the ORR1A0 LTR produced a chimeric mRNA with Pu.1 that, in turn, encoded a truncated protein isoform called PU.2 (bottom) lacking the N-terminal activation domain of PU.1. PU.2 retained its DNA binding capacity, but did not interact with other transcription factors, leading to a putative role as a dominant negative isoform of PU.1 promoting erythroid maturation.