Identification of an alternatively spliced form of the mouse AML1/RUNX1 gene transcript AML1c and its expression in early hematopoietic development

Acute myeloid leukemia 1 (AML1: or runt-related transcription factor, RUNX1 ) encodes the DNA binding subunit of the heterodimering transcription facto r complex PEEP2 (CBF), which plays an essential role for definitive hematop oiesis. Transcription of AML1 is controlled by two distinct promoter region s, which results in the generation of the respective AML1b and AML1c isofor ms. Here we report the isolation of the mouse homologue of human AML1c, who se unique N-terminus is 100% identical at the amino acid level to its human counterpart and 63 and 37% identical to the respective family members AML2 and AML3. Semiquantitative RT-PCR assay on mouse embryonic stem cell clone s during in vitro differentiation and Northern blot analysis of a mouse emb ryo revealed that AML1b is expressed in undifferentiated ES cells and upreg ulated in the early developmental stage, in contrast to the gradual upregul ation and steady maintenance of AML1c expression during embryogenesis. In a ddition, maintenance of AML1c expression depended on the presence of active AML1 allele(s) while that of AML1b did not. Thus, these two AML1 isoforms driven by their respective promoters are differentially expressed and are l ikely to have distinct functions in early hematopoietic development. (C) 20 01 Academic Press.