We herein described how lineage-specific transcription factor GATA-1 inhibits PU. 1 gene expression in human AML-EL cells and identified an as-yet unknown mechanism involving DNMT1, which co-occupies with GATA-1 at the PU.1 locus, specifically, at the URE that regulates most of the PU.1 expression. Here, GATA1 is linked to acute myeloid leukemia.